Olaparib in gBRCA Mutated Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy  (POLO)

Recruitment Status:
Active, not recruiting

Sponsor:
AstraZeneca

Collaborator:
Myriad Genetics - BRCAnalysis test for FDA Premarket Approval (PMA)
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Information Provided by (Responsible Party):
AstraZeneca

ClinicalTrials.gov Identifier:
NCT02184195

Verification:
Verified 01 January 2020   by AstraZeneca

History of Changes:
ClinicalTrials.gov

Purpose

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre
Study of Maintenance Olaparib Monotherapy in Patients with gBRCA
Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on
First Line Platinum Based Chemotherapy

Official Title:A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy
Study Type:Interventional
Overall Recruitment Status:Active, not recruiting
Study Start Date:16 December 2014
Study Start Date Type:Actual
Primary Completion Date:15 January 2019
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind   (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
ConditionInterventionPhase
germline BRCA1/2 mutations and
metastatic adenocarcinoma of the pancreas
Drug: Olaparib
Drug: Olaparib
Drug: Placebo
Drug: Placebo
Phase 3
Ages Eligible for Study: 18 Years  to 130 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:
-Histologically or cytologically confirmed pancreas adenocarcinoma receiving initial chemotherapy for metastatic disease and without evidence of disease progression on treatment
-Patients with measurable disease and/or non-measurable or no evidence of disease
assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in
this study.
-Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or
suspected deleterious
- Patients are on treatment with a first line platinum-based (cisplatin, carboplatin or
oxaliplatin) regimen for metastatic pancreas cancer, have received a minimum of 16
weeks of continuous platinum treatment and have no evidence of progression based
on investigator’s opinion.
-Patients who have received platinum as potentially curative treatment for a prior
cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer
are eligible provided at least 12 months have elapsed between the last dose of
platinum-based treatment and initiation of the platinum-based chemotherapy for
metastatic pancreas cancer.

Major Exclusion Criteria:
-gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg,
“Variants of uncertain clinical significance” or “Variant of unknown significance”
or “Variant, favour polymorphism” or “benign polymorphism” etc.)
-Progression of tumour between start of first line platinum based chemotherapy for
metastatic pancreas cancer and randomisation.
-Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle
1 Day 1 is not permitted.
-Exposure to an investigational product within 30 days or 5 half lives (whichever is
longer) prior to randomisation
-Any previous treatment with a PARP inhibitor, including Olaparib


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    information.center@astrazeneca.com  
Contact Backup: AstraZeneca Cancer Study  Locator Service   1-877-400-4656    astrazeneca@emergingmed.com  

Sponsors and Collaborators

AstraZeneca
Myriad Genetics - BRCAnalysis test for FDA Premarket Approval (PMA)
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.


Locations

CountryLocationFacilityContactStatus
BelgiumResearch Site Antwerpen, Belgium, 2020Completed
BelgiumResearch Site Brussels (Anderlecht), Belgium, 1070Completed
BelgiumResearch Site Edegem, Belgium, 2650Withdrawn
BelgiumResearch Site Leuven, Belgium, 3000Active, not recruiting
CanadaResearch Site Toronto, Canada, M5G 2M9Completed
GermanyResearch Site Berlin, Germany, 10967Active, not recruiting
GermanyResearch Site Berlin, Germany, D-13353Completed
GermanyResearch Site Bochum, Germany, 44791Active, not recruiting
GermanyResearch Site Bonn, Germany, 53127Completed
GermanyResearch Site Dresden, Germany, 01307Completed
GermanyResearch Site Frankfurt am Main, Germany, 60596Completed
GermanyResearch Site Freiburg im Breisgau, Germany, 79106Withdrawn
GermanyResearch Site Hamburg, Germany, 22291Completed
GermanyResearch Site Hamburg, Germany, 20246Completed
GermanyResearch Site Hannover, Germany, 30625Completed
GermanyResearch Site Leipzig, Germany, 04103Completed
GermanyResearch Site München, Germany, 81675Active, not recruiting
GermanyResearch Site Schweinfurt, Germany, 97422Completed
GermanyResearch Site Ulm, Germany, 89081Completed
AustraliaResearch Site Campbelltown, Australia, 2560Completed
AustraliaResearch Site Lilydale, Australia, 3140Withdrawn
AustraliaResearch Site Randwick, Australia, 2031Active, not recruiting
AustraliaResearch Site St Leonards, Australia, 2065Completed
AustraliaResearch Site Woolloongabba, Australia, 4102Withdrawn
Canada , ONResearch Site London, ON, Canada, N6A 4L6Completed
Canada , ONResearch Site Ottawa, ON, Canada, K1H 8L6Withdrawn
FranceResearch Site Amiens, France, 80054Completed
FranceResearch Site Besançon, France, 25030Completed
FranceResearch Site Bordeaux, France, 33075Active, not recruiting
FranceResearch Site Brest Cedex, France, 29609Completed
FranceResearch Site Clichy Cedex, France, 92118Active, not recruiting
FranceResearch Site La Roche sur Yon, France, 85925Completed
FranceResearch Site LILLE, France, 59020Active, not recruiting
FranceResearch Site Lyon, France, 69008Withdrawn
FranceResearch Site LYON CEDEX 03, France, 69437Active, not recruiting
FranceResearch Site Montpellier, France, 34298Withdrawn
FranceResearch Site Nice, France, 06189Completed
FranceResearch Site PARIS, France, 75014Completed
FranceResearch Site Paris CEDEX 14, France, 75674Completed
FranceResearch Site POITIERS, France, 86021Active, not recruiting
FranceResearch Site Rennes, France, 35042Withdrawn
FranceResearch Site STRASBOURG Cedex, France, 67065Completed
FranceResearch Site Toulouse, France, 31059Completed
FranceResearch Site Villejuif, France, 94800Active, not recruiting
IsraelResearch Site Beer Sheva, Israel, 84101Completed
IsraelResearch Site Haifa, Israel, 3109601Completed
IsraelResearch Site Holon, Israel, 58100Completed
IsraelResearch Site Nahariya, Israel, 22100Active, not recruiting
IsraelResearch Site Petah Tikva, Israel, 4941492Active, not recruiting
IsraelResearch Site Ramat Gan, Israel, 5265601Active, not recruiting
IsraelResearch Site Rehovot, Israel, 76100Completed
IsraelResearch Site Tel-Aviv, Israel, 6423906Active, not recruiting
IsraelResearch Site Zefir, Israel, 7030000Completed
SpainResearch Site Barcelona, Spain, 08035Active, not recruiting
SpainResearch Site Girona, Spain, 17007Active, not recruiting
SpainResearch Site L'Hospitalet de Llobregat, Spain, 08907Completed
SpainResearch Site Madrid, Spain, 28007Completed
SpainResearch Site Madrid, Spain, 28034Completed
SpainResearch Site Madrid, Spain, 28050Completed
SpainResearch Site Madrid, Spain, 28041Active, not recruiting
SpainResearch Site Málaga, Spain, 29010Completed
SpainResearch Site Pamplona, Spain, 31008Active, not recruiting
SpainResearch Site Sabadell, Spain, 8208Completed
SpainResearch Site Santiago de Compostela, Spain, 15706Completed
SpainResearch Site Valencia, Spain, 46009Completed
SpainResearch Site Zaragoza, Spain, 50009Completed
United KingdomResearch Site Edinburgh, United Kingdom, EH4 2XRCompleted
United KingdomResearch Site Glasgow, United Kingdom, G12 0YNCompleted
United KingdomResearch Site Leeds, United Kingdom, LS9 7TFWithdrawn
United KingdomResearch Site Liverpool, United Kingdom, L69 3GAActive, not recruiting
United KingdomResearch Site London, United Kingdom, WC1E 6AGCompleted
United KingdomResearch Site London, United Kingdom, SE5 9RSCompleted
United KingdomResearch Site Manchester, United Kingdom, M20 4BXCompleted
United KingdomResearch Site Northwood, United Kingdom, HA6 2RNCompleted
United KingdomResearch Site Nottingham, United Kingdom, NG5 1PBCompleted
United KingdomResearch Site Surrey, United Kingdom, SM1 2DLActive, not recruiting
South KoreaResearch Site Seongnam-si, South Korea, 13620Completed
South KoreaResearch Site Seoul, South Korea, 03080Active, not recruiting
South KoreaResearch Site Seoul, South Korea, 6351Active, not recruiting
NetherlandsResearch Site Amsterdam, Netherlands, 1105 AZActive, not recruiting
NetherlandsResearch Site Maastricht, Netherlands, 6202 AZWithdrawn
United States of America , CAResearch Site Downey, CA, United States of America, 90241Withdrawn
United States of America , CAResearch Site La Jolla, CA, United States of America, 92093Withdrawn
United States of America , CAResearch Site Los Angeles, CA, United States of America, 90048Withdrawn
United States of America , CAResearch Site Los Angeles, CA, United States of America, 90030Withdrawn
United States of America , CAResearch Site Santa Monica, CA, United States of America, 90404Withdrawn
United States of America , CAResearch Site Stanford, CA, United States of America, 94305-5720Active, not recruiting
Canada , QCResearch Site Montreal, QC, Canada, H2X 3J4Withdrawn
Canada , QCResearch Site Sherbrooke, QC, Canada, J1G 2E8Completed
ItalyResearch Site Ancona, Italy, 60126Withdrawn
ItalyResearch Site Bologna, Italy, 40138Completed
ItalyResearch Site Milano, Italy, 20132Active, not recruiting
ItalyResearch Site Milano, Italy, 20133Completed
ItalyResearch Site Monserrato, Italy, 09042Withdrawn
ItalyResearch Site PADOVA, Italy, 35128Completed
ItalyResearch Site Parma, Italy, 43126Completed
ItalyResearch Site Pescara, Italy, 65100Completed
ItalyResearch Site Pisa, Italy, 56126Withdrawn
ItalyResearch Site Roma, Italy, 00144Active, not recruiting
ItalyResearch Site Roma, Italy, 00128Completed
ItalyResearch Site San Giovanni Rotondo, Italy, 71013Active, not recruiting
ItalyResearch Site Verona, Italy, 37134Active, not recruiting
United States of America , ILResearch Site Chicago, IL, United States of America, 60637Active, not recruiting
United States of America , ILResearch Site Evanston, IL, United States of America, 60201Withdrawn
United States of America , MDResearch Site Baltimore, MD, United States of America, 21287Active, not recruiting
United States of America , MDResearch Site Bethesda, MD, United States of America, 20889Withdrawn
United States of America , PAResearch Site Philadelphia, PA, United States of America, 19111Completed
United States of America , ConnecticutResearch Site New Haven, Connecticut, United States of America, 06510-3220Completed
United States of America , OHResearch Site Columbus, OH, United States of America, 43210Completed
United States of America , COResearch Site Aurora, CO, United States of America, 80045Completed
United States of America , FLResearch Site Boca Raton, FL, United States of America, 33486Active, not recruiting
United States of America , FLResearch Site Miami, FL, United States of America, 33136Withdrawn
United States of America , FLResearch Site Miami, FL, United States of America, 33136Active, not recruiting
United States of America , NYResearch Site Commack, NY, United States of America, 11725Completed
United States of America , NYResearch Site New York, NY, United States of America, 10032Completed
United States of America , NYResearch Site New York, NY, United States of America, 10022Active, not recruiting
United States of America , NYResearch Site New York, NY, United States of America, 10065Completed
United States of America , NYResearch Site Sleepy Hollow, NY, United States of America, 10591Withdrawn
United States of America , NYResearch Site West Harrison, NY, United States of America, 10604Withdrawn
United States of America , MOResearch Site St Louis, MO, United States of America, 63110Completed
United States of America , SCResearch Site Spartenburg, SC, United States of America, 29303Withdrawn
Canada , QuebecResearch Site Montreal, Quebec, Canada, H3T 1E2Completed
United States of America , ArizonaResearch Site Gilbert, Arizona, United States of America, 85234Completed
United States of America , CaliforniaResearch Site Orange, California, United States of America, 92868-3298Completed
United States of America , MAResearch Site Boston, MA, United States of America, 02114-2696Withdrawn
United States of America , MAResearch Site Boston, MA, United States of America, 02215Active, not recruiting
United States of America , WAResearch Site Seattle, WA, United States of America, 98109Withdrawn
United States of America , WAResearch Site Seattle, WA, United States of America, 98104Completed
Canada , MBResearch Site Winnipeg, MB, Canada, R2H 2A6Withdrawn
United States of America , TXResearch Site Arlington, TX, United States of America, 76012Withdrawn
United States of America , TXResearch Site Dallas, TX, United States of America, 75390Withdrawn
United States of America , TXResearch Site Houston, TX, United States of America, 77030Active, not recruiting
United States of America , New YorkResearch Site New York City, New York, United States of America, 10015Completed
United States of America , New YorkResearch Site Rockville Centre, New York, United States of America, 11570-1000Withdrawn
United States of America , NJResearch Site Basking Ridge, NJ, United States of America, 07920Withdrawn
United States of America , DCResearch Site Washington, DC, United States of America, 20007Withdrawn

Participant Flow


Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study randomised patients at a total of 59 study centres in 12 countries: United States of America (13), Germany (8), France (7), Israel (7), Spain (7), United Kingdom (6), Italy (4), Belgium (2), Republic of Korea (2), Australia (1), Canada (1) and Netherlands (1).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening Part 1 was only required if a patient’s gBRCAm status was unknown and Screening Part 2 was for patients with known local germline BRCA (gBRCA) test. All other screening parameters were done as per the Study Schedule.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Participant Flow:   Overall Study

 Olaparib 300 mg twice daily (bd)Placebo
 STARTED 9262
 COMPLETED 4927
 NOT COMPLETED 4335
  Patient decision  31
  Eligibility criteria not fulfilled  01
  Death  4029
  Lost to Follow-up  02
  Other  02

Baseline Characteristics


Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

Description
Olaparib 300 mg twice daily (bd)
Placebo

Baseline Measures

 Olaparib 300 mg twice daily (bd)PlaceboTotal
Number of Participants
[units: Participants]
9262154
Age Continuous
[units: Years]
Mean ± Standard Deviation
58.2 ± 10.2756.4 ± 9.0757.5 ± 9.81
Sex: Female, Male
[units: Participants]
   
Female393170
Male533184
Race (NIH/OMB)
[units: Participants]
   
American Indian or Alaska Native101
Asian426
Native Hawaiian or Other Pacific Islander000
Black or African American505
White8259141
More than one race000
Unknown or Not Reported011
Ethnicity (NIH/OMB)
[units: Participants]
   
Hispanic or Latino426
Not Hispanic or Latino8860148
Unknown or Not Reported000

Outcome Measures


1. Primary Outcome Measure: Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)   [ Time Frame: Up to 4 years ]

Measure TypePrimary
Measure NameProgression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)
Measure DescriptionTo determine the efficacy of olaparib maintenance monotherapy compared to placebo by PFS. The PFS was defined as the time from randomisation until the date of objective radiological disease progression according to modified RECIST v1.1 or death (by any cause in the absence of disease progression) regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to disease progression.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)
[units: Months]
Median (95% Confidence Interval)
7.4 (4.14 to 11.01) 3.8 (3.52 to 4.86)

Statistical Analysis 1 for Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.0038
Hazard Ratio (HR)  [5] 0.531
95% Confidence Interval( 0.346 to 0.815 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
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[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[5]  Other relevant estimation information:
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2. Secondary Outcome Measure: Overall Survival (OS)   [ Time Frame: Upto 4 years ]

Measure TypeSecondary
Measure NameOverall Survival (OS)
Measure DescriptionTo determine the efficacy by assessment of OS of olaparib maintenance monotherapy compared to placebo. The OS was defined as the time from the date of randomization until death due to any cause.
Time FrameUpto 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Overall Survival (OS)
[units: Months]
Median (95% Confidence Interval)
18.9 (14.85 to 26.15) 18.1 (12.62 to 26.12)

Statistical Analysis 1 for Overall Survival (OS)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.6833
Hazard Ratio (HR)  [5] 0.906
95% Confidence Interval( 0.563 to 1.457 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
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3. Secondary Outcome Measure: Time from randomisation to second progression (PFS2)   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameTime from randomisation to second progression (PFS2)
Measure DescriptionTo determine efficacy by assessment of PFS2 of olaparib maintenance monotherapy compared to placebo. The PFS2 was defined as the time from the date of randomisation to the earliest of the progression event subsequent to that used for the primary variable PFS or death.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Time from randomisation to second progression (PFS2)
[units: Months]
Median (95% Confidence Interval)
13.2 (7.75 to 26.15) 9.2 (7.62 to 13.54)

Statistical Analysis 1 for Time from randomisation to second progression (PFS2)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.2597
Hazard Ratio (HR)  [5] 0.755
95% Confidence Interval( 0.464 to 1.230 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
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4. Secondary Outcome Measure: Time from randomisation to second subsequent therapy or death (TSST)   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameTime from randomisation to second subsequent therapy or death (TSST)
Measure DescriptionTo determine the efficacy by assessment of TSST of olaparib maintenance monotherapy compared to placebo. The TSST was defined as time to second subsequent therapy or death.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Time from randomisation to second subsequent therapy or death (TSST)
[units: Months]
Median (95% Confidence Interval)
13.2 (8.84 to 20.04) 9.2 (8.34 to 13.14)

Statistical Analysis 1 for Time from randomisation to second subsequent therapy or death (TSST)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.0825
Hazard Ratio (HR)  [5] 0.678
95% Confidence Interval( 0.437 to 1.051 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

5. Secondary Outcome Measure: Time from randomisation to first subsequent therapy or death (TFST)   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameTime from randomisation to first subsequent therapy or death (TFST)
Measure DescriptionTo determine the efficacy by assessment of TFST of olaparib maintenance monotherapy compared to placebo. The TFST was defined as time to first subsequent therapy or death.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Time from randomisation to first subsequent therapy or death (TFST)
[units: Months]
Median (95% Confidence Interval)
8.6 (6.21 to 12.45) 5.7 (4.17 to 6.34)

Statistical Analysis 1 for Time from randomisation to first subsequent therapy or death (TFST)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.0013
Hazard Ratio (HR)  [5] 0.496
95% Confidence Interval( 0.324 to 0.760 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

6. Secondary Outcome Measure: Time from randomisation to study treatment discontinuation or death (TDT)   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameTime from randomisation to study treatment discontinuation or death (TDT)
Measure DescriptionTo determine the efficacy by assessment of TDT compared to placebo. compared to placebo. The TDT was defined as time to study treatment discontinuation or death.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Number of Full Analyisis Set Analyzed
Time from randomisation to study treatment discontinuation or death (TDT)
[units: Months]
Median (95% Confidence Interval)
7.2 (5.52 to 10.84) 3.8 (3.55 to 4.80)

Statistical Analysis 1 for Time from randomisation to study treatment discontinuation or death (TDT)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.0001
Hazard Ratio (HR)  [5] 0.446
95% Confidence Interval( 0.297 to 0.670 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

7. Secondary Outcome Measure: Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameNumber of participants with objective response rate (ORR) by BICR using modified RECIST 1.1
Measure DescriptionTo determine efficacy by assessment of objective response rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo. The ORR is defined as the number of with a BoR of CR and PR according to the BICR data divided by the number of patients in the treatment group with measurable disease at baseline.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients (patients with measurable disease at baseline).

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1
[units: Participants with response]
186

Statistical Analysis 1 for Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1

Groups  [1] All groups
Method  [3] Regression, Logistic
P-Value  [4] 0.1028
Odds Ratio (OR)  [5] 2.300
95% Confidence Interval( 0.886 to 6.761 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

8. Secondary Outcome Measure: Disease control rate (DCR) by BICR using modified RECIST 1.1   [ Time Frame: At 16 weeks ]

Measure TypeSecondary
Measure NameDisease control rate (DCR) by BICR using modified RECIST 1.1
Measure DescriptionEfficacy by assessment of disease control rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo.
Time FrameAt 16 weeks
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Disease control rate (DCR) by BICR using modified RECIST 1.1
[units: Participants]
  
Yes4923
Yes4135
Yes24

No statistical analysis provided for Disease control rate (DCR) by BICR using modified RECIST 1.1

9. Secondary Outcome Measure: Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire   [ Time Frame: From baseline up to 6 months ]

Measure TypeSecondary
Measure NameAdjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire
Measure DescriptionTo assess the effect of olaparib on health-related quality of life (QoL) as measured by the EORTC-QLQ-C30 global QoL scale. The EORTC-QLQ-C30 is defined as EORTC QLQ-C30: a questionnaire (30 questions) used to evaluate disease symptoms, functional impacts (eg, physical functioning), and HRQoL and to characterize clinical benefit from the patient perspective. The HRQoL score ranges from 0 to 100. A higher score indicates better QoL. A score change of 10 points was pre-defined as clinically meaningful. bd twice daily.
Time FrameFrom baseline up to 6 months
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patient reported outcome (PRO) analysis set was defined as the analysis population for PRO data were a subset of the FAS (ITT) population who had evaluable baseline EORTC QLQ-C30 or QLQ-PAN26 forms where evaluable meant that at least 1 sub-scale baseline score could be determined from at least 1 of the 2 forms.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
8958
Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire
[units: Unit on scale]
Mean (95% Confidence Interval)
-1.20 (-4.014 to 1.618) 1.27 (-2.580 to 5.124)

Statistical Analysis 1 for Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire

Groups  [1] All groups
Method  [3] Mixed Models Analysis
P-Value  [4] 0.310
Mean Difference (Final Values)  [5] -2.47
95% Confidence Interval( -7.267 to 2.327 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

10. Secondary Outcome Measure: Number of participants with adverse events (AEs)   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameNumber of participants with adverse events (AEs)
Measure DescriptionTo assess the safety and tolerability of olaparib maintenance monotherapy. SAE: serious adverse events CTCAE: Common Terminology Criteria for Adverse Events
Time FrameUp to 4 years
Safety Issue?Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9160
Number of participants with adverse events (AEs)
[units: Participants]
  
Any AE8756
Any AE3614
Any AE00
Any AE229
Any AE51
Any AE323
Any AE152

No statistical analysis provided for Number of participants with adverse events (AEs)

Serious Adverse Events


Time FrameScreening to follow-up visit (30-day follow-up)
Additional DescriptionNo text entered.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Serious Adverse Events

 Olaparib 300 mg twice daily (bd)Placebo
Total, serious adverse events   
# participants affected / at risk 22/91 (24.18%)9/60 (15.00%)
Infections and infestations  
Abdominal infection1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Infections and infestations  
Bartholinitis1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Infections and infestations  
Pneumonia1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Infections and infestations  
Urinary tract infection1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Blood and lymphatic system disorders  
Anaemia1  
# participants affected / at risk 6/91 (6.59%)0/60 (0.00%)
Blood and lymphatic system disorders  
Febrile Neutropenia1  
# participants affected / at risk 0/91 (0.00%)1/60 (1.67%)
Endocrine disorders  
Hypothyroidism1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Metabolism and nutrition disorders  
Decreased appetite1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Metabolism and nutrition disorders  
Hyperglycaemia1  
# participants affected / at risk 0/91 (0.00%)1/60 (1.67%)
Nervous system disorders  
Cerebrovascular accident1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Nervous system disorders  
Embolic stroke1  
# participants affected / at risk 0/91 (0.00%)1/60 (1.67%)
Nervous system disorders  
Transient ischaemic attack1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Cardiac disorders  
Cardiac failure1  
# participants affected / at risk 1/91 (1.10%)1/60 (1.67%)
Vascular disorders  
Vascular stenosis1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Respiratory, thoracic and mediastinal disorders  
Pleural effusion1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Respiratory, thoracic and mediastinal disorders  
Pneumothorax1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Abdominal pain1  
# participants affected / at risk 3/91 (3.30%)1/60 (1.67%)
Gastrointestinal disorders  
Constipation1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Duodenal perforation1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Gastric varices haemorrhage1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Incarcerated inguinal hernia1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Large intestinal obstruction1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Melaena1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Obstruction gastric1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Pancreatitis1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Vomiting1  
# participants affected / at risk 1/91 (1.10%)3/60 (5.00%)
Hepatobiliary disorders  
Bile duct obstruction1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Hepatobiliary disorders  
Cholangitis1  
# participants affected / at risk 2/91 (2.20%)1/60 (1.67%)
Hepatobiliary disorders  
Cholecystitis1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
General disorders  
General physical health deterioration1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Investigations  
Platelet count decreased1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Injury, poisoning and procedural complications  
Anastomotic haemorrhage1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Product Issues  
Device occlusion1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Product Issues  
Stent malfunction1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
General disorders  
Pyrexia1  
# participants affected / at risk 0/91 (0.00%)2/60 (3.33%)
Events were collected by systematic assessment
1Term from vocabulary,  MedDRA version 21.1

Other Adverse Events


Time FrameScreening to follow-up visit (30-day follow-up)
Additional DescriptionNo text entered.

Frequency Threshold

Threshold above which other adverse events are reported 5%

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Other Adverse Events

 Olaparib 300 mg twice daily (bd)Placebo
Total, other (not including serious) adverse events   
# participants affected / at risk 87/91 (95.60%)56/60 (93.33%)
Gastrointestinal disorders  
Nausea1  
# participants affected / at risk 41/91 (45.05%)14/60 (23.33%)
Gastrointestinal disorders  
Diarrhoea1  
# participants affected / at risk 26/91 (28.57%)9/60 (15.00%)
Gastrointestinal disorders  
Abdominal pain1  
# participants affected / at risk 23/91 (25.27%)14/60 (23.33%)
Gastrointestinal disorders  
Constipation1  
# participants affected / at risk 20/91 (21.98%)6/60 (10.00%)
Gastrointestinal disorders  
Vomiting1  
# participants affected / at risk 18/91 (19.78%)8/60 (13.33%)
Gastrointestinal disorders  
Stomatitis1  
# participants affected / at risk 7/91 (7.69%)3/60 (5.00%)
Gastrointestinal disorders  
Abdominal pain upper1  
# participants affected / at risk 6/91 (6.59%)8/60 (13.33%)
Gastrointestinal disorders  
Dry mouth1  
# participants affected / at risk 6/91 (6.59%)1/60 (1.67%)
Gastrointestinal disorders  
Dyspepsia1  
# participants affected / at risk 5/91 (5.49%)5/60 (8.33%)
Gastrointestinal disorders  
Abdominal distension1  
# participants affected / at risk 4/91 (4.40%)6/60 (10.00%)
Gastrointestinal disorders  
Flatulence1  
# participants affected / at risk 2/91 (2.20%)4/60 (6.67%)
General disorders  
Fatigue1  
# participants affected / at risk 41/91 (45.05%)16/60 (26.67%)
General disorders  
Asthenia1  
# participants affected / at risk 15/91 (16.48%)5/60 (8.33%)
General disorders  
Pyrexia1  
# participants affected / at risk 12/91 (13.19%)3/60 (5.00%)
General disorders  
Oedema peripheral1  
# participants affected / at risk 8/91 (8.79%)5/60 (8.33%)
Musculoskeletal and connective tissue disorders  
Back pain1  
# participants affected / at risk 17/91 (18.68%)10/60 (16.67%)
Musculoskeletal and connective tissue disorders  
Arthralgia1  
# participants affected / at risk 14/91 (15.38%)6/60 (10.00%)
Musculoskeletal and connective tissue disorders  
Muscle spasms1  
# participants affected / at risk 6/91 (6.59%)2/60 (3.33%)
Musculoskeletal and connective tissue disorders  
Pain in extremity1  
# participants affected / at risk 6/91 (6.59%)4/60 (6.67%)
Musculoskeletal and connective tissue disorders  
Musculoskeletal pain1  
# participants affected / at risk 5/91 (5.49%)3/60 (5.00%)
Musculoskeletal and connective tissue disorders  
Myalgia1  
# participants affected / at risk 5/91 (5.49%)3/60 (5.00%)
Musculoskeletal and connective tissue disorders  
Flank pain1  
# participants affected / at risk 1/91 (1.10%)4/60 (6.67%)
Nervous system disorders  
Dysgeusia1  
# participants affected / at risk 10/91 (10.99%)3/60 (5.00%)
Nervous system disorders  
Neuropathy peripheral1  
# participants affected / at risk 7/91 (7.69%)7/60 (11.67%)
Nervous system disorders  
Dizziness1  
# participants affected / at risk 6/91 (6.59%)3/60 (5.00%)
Nervous system disorders  
Headache1  
# participants affected / at risk 6/91 (6.59%)8/60 (13.33%)
Nervous system disorders  
Peripheral sensory neuropathy1  
# participants affected / at risk 6/91 (6.59%)2/60 (3.33%)
Blood and lymphatic system disorders  
Anaemia1  
# participants affected / at risk 23/91 (25.27%)10/60 (16.67%)
Blood and lymphatic system disorders  
Neutropenia1  
# participants affected / at risk 7/91 (7.69%)4/60 (6.67%)
Blood and lymphatic system disorders  
Thrombocytopenia1  
# participants affected / at risk 7/91 (7.69%)4/60 (6.67%)
Metabolism and nutrition disorders  
Decreased appetite1  
# participants affected / at risk 22/91 (24.18%)4/60 (6.67%)
Metabolism and nutrition disorders  
Hyperglycaemia1  
# participants affected / at risk 8/91 (8.79%)1/60 (1.67%)
Skin and subcutaneous tissue disorders  
Rash1  
# participants affected / at risk 11/91 (12.09%)2/60 (3.33%)
Skin and subcutaneous tissue disorders  
Pruritus1  
# participants affected / at risk 9/91 (9.89%)4/60 (6.67%)
Investigations  
Alanine aminotransferase increased1  
# participants affected / at risk 8/91 (8.79%)1/60 (1.67%)
Investigations  
Aspartate aminotransferase increased1  
# participants affected / at risk 6/91 (6.59%)1/60 (1.67%)
Investigations  
Blood creatinine increased1  
# participants affected / at risk 6/91 (6.59%)1/60 (1.67%)
Investigations  
Blood alkaline phosphatase increased1  
# participants affected / at risk 5/91 (5.49%)3/60 (5.00%)
Investigations  
Platelet count decreased1  
# participants affected / at risk 5/91 (5.49%)0/60 (0.00%)
Psychiatric disorders  
Insomnia1  
# participants affected / at risk 7/91 (7.69%)1/60 (1.67%)
Psychiatric disorders  
Anxiety1  
# participants affected / at risk 5/91 (5.49%)2/60 (3.33%)
Psychiatric disorders  
Depression1  
# participants affected / at risk 5/91 (5.49%)0/60 (0.00%)
Respiratory, thoracic and mediastinal disorders  
Dyspnoea1  
# participants affected / at risk 10/91 (10.99%)3/60 (5.00%)
Respiratory, thoracic and mediastinal disorders  
Cough1  
# participants affected / at risk 8/91 (8.79%)2/60 (3.33%)
Infections and infestations  
Nasopharyngitis1  
# participants affected / at risk 11/91 (12.09%)2/60 (3.33%)
Infections and infestations  
Influenza1  
# participants affected / at risk 5/91 (5.49%)0/60 (0.00%)
Events were collected by systematic assessment
1Term from vocabulary,  MedDRA version 21.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:Global Clinical Leader
Organization:AstraZeneca AB
Phone1-877-240-9479 
E-mail:information.center@astrazeneca.com
.

Purpose

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre
Study of Maintenance Olaparib Monotherapy in Patients with gBRCA
Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on
First Line Platinum Based Chemotherapy

Official Title:A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy
Study Type:Interventional
Overall Recruitment Status:Active, not recruiting
Study Start Date:16 December 2014
Study Start Date Type:Actual
Primary Completion Date:15 January 2019
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind   (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
ConditionInterventionPhase
germline BRCA1/2 mutations and
metastatic adenocarcinoma of the pancreas
Drug: Olaparib
Drug: Olaparib
Drug: Placebo
Drug: Placebo
Phase 3
Ages Eligible for Study: 18 Years  to 130 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:
-Histologically or cytologically confirmed pancreas adenocarcinoma receiving initial chemotherapy for metastatic disease and without evidence of disease progression on treatment
-Patients with measurable disease and/or non-measurable or no evidence of disease
assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in
this study.
-Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or
suspected deleterious
- Patients are on treatment with a first line platinum-based (cisplatin, carboplatin or
oxaliplatin) regimen for metastatic pancreas cancer, have received a minimum of 16
weeks of continuous platinum treatment and have no evidence of progression based
on investigator’s opinion.
-Patients who have received platinum as potentially curative treatment for a prior
cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer
are eligible provided at least 12 months have elapsed between the last dose of
platinum-based treatment and initiation of the platinum-based chemotherapy for
metastatic pancreas cancer.

Major Exclusion Criteria:
-gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg,
“Variants of uncertain clinical significance” or “Variant of unknown significance”
or “Variant, favour polymorphism” or “benign polymorphism” etc.)
-Progression of tumour between start of first line platinum based chemotherapy for
metastatic pancreas cancer and randomisation.
-Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle
1 Day 1 is not permitted.
-Exposure to an investigational product within 30 days or 5 half lives (whichever is
longer) prior to randomisation
-Any previous treatment with a PARP inhibitor, including Olaparib


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    information.center@astrazeneca.com  
Contact Backup: AstraZeneca Cancer Study  Locator Service   1-877-400-4656    astrazeneca@emergingmed.com  

Sponsors and Collaborators

AstraZeneca
Myriad Genetics - BRCAnalysis test for FDA Premarket Approval (PMA)
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.


Locations

CountryLocationFacilityContactStatus
BelgiumResearch Site Antwerpen, Belgium, 2020Completed
BelgiumResearch Site Brussels (Anderlecht), Belgium, 1070Completed
BelgiumResearch Site Edegem, Belgium, 2650Withdrawn
BelgiumResearch Site Leuven, Belgium, 3000Active, not recruiting
CanadaResearch Site Toronto, Canada, M5G 2M9Completed
GermanyResearch Site Berlin, Germany, 10967Active, not recruiting
GermanyResearch Site Berlin, Germany, D-13353Completed
GermanyResearch Site Bochum, Germany, 44791Active, not recruiting
GermanyResearch Site Bonn, Germany, 53127Completed
GermanyResearch Site Dresden, Germany, 01307Completed
GermanyResearch Site Frankfurt am Main, Germany, 60596Completed
GermanyResearch Site Freiburg im Breisgau, Germany, 79106Withdrawn
GermanyResearch Site Hamburg, Germany, 22291Completed
GermanyResearch Site Hamburg, Germany, 20246Completed
GermanyResearch Site Hannover, Germany, 30625Completed
GermanyResearch Site Leipzig, Germany, 04103Completed
GermanyResearch Site München, Germany, 81675Active, not recruiting
GermanyResearch Site Schweinfurt, Germany, 97422Completed
GermanyResearch Site Ulm, Germany, 89081Completed
AustraliaResearch Site Campbelltown, Australia, 2560Completed
AustraliaResearch Site Lilydale, Australia, 3140Withdrawn
AustraliaResearch Site Randwick, Australia, 2031Active, not recruiting
AustraliaResearch Site St Leonards, Australia, 2065Completed
AustraliaResearch Site Woolloongabba, Australia, 4102Withdrawn
Canada , ONResearch Site London, ON, Canada, N6A 4L6Completed
Canada , ONResearch Site Ottawa, ON, Canada, K1H 8L6Withdrawn
FranceResearch Site Amiens, France, 80054Completed
FranceResearch Site Besançon, France, 25030Completed
FranceResearch Site Bordeaux, France, 33075Active, not recruiting
FranceResearch Site Brest Cedex, France, 29609Completed
FranceResearch Site Clichy Cedex, France, 92118Active, not recruiting
FranceResearch Site La Roche sur Yon, France, 85925Completed
FranceResearch Site LILLE, France, 59020Active, not recruiting
FranceResearch Site Lyon, France, 69008Withdrawn
FranceResearch Site LYON CEDEX 03, France, 69437Active, not recruiting
FranceResearch Site Montpellier, France, 34298Withdrawn
FranceResearch Site Nice, France, 06189Completed
FranceResearch Site PARIS, France, 75014Completed
FranceResearch Site Paris CEDEX 14, France, 75674Completed
FranceResearch Site POITIERS, France, 86021Active, not recruiting
FranceResearch Site Rennes, France, 35042Withdrawn
FranceResearch Site STRASBOURG Cedex, France, 67065Completed
FranceResearch Site Toulouse, France, 31059Completed
FranceResearch Site Villejuif, France, 94800Active, not recruiting
IsraelResearch Site Beer Sheva, Israel, 84101Completed
IsraelResearch Site Haifa, Israel, 3109601Completed
IsraelResearch Site Holon, Israel, 58100Completed
IsraelResearch Site Nahariya, Israel, 22100Active, not recruiting
IsraelResearch Site Petah Tikva, Israel, 4941492Active, not recruiting
IsraelResearch Site Ramat Gan, Israel, 5265601Active, not recruiting
IsraelResearch Site Rehovot, Israel, 76100Completed
IsraelResearch Site Tel-Aviv, Israel, 6423906Active, not recruiting
IsraelResearch Site Zefir, Israel, 7030000Completed
SpainResearch Site Barcelona, Spain, 08035Active, not recruiting
SpainResearch Site Girona, Spain, 17007Active, not recruiting
SpainResearch Site L'Hospitalet de Llobregat, Spain, 08907Completed
SpainResearch Site Madrid, Spain, 28007Completed
SpainResearch Site Madrid, Spain, 28034Completed
SpainResearch Site Madrid, Spain, 28050Completed
SpainResearch Site Madrid, Spain, 28041Active, not recruiting
SpainResearch Site Málaga, Spain, 29010Completed
SpainResearch Site Pamplona, Spain, 31008Active, not recruiting
SpainResearch Site Sabadell, Spain, 8208Completed
SpainResearch Site Santiago de Compostela, Spain, 15706Completed
SpainResearch Site Valencia, Spain, 46009Completed
SpainResearch Site Zaragoza, Spain, 50009Completed
United KingdomResearch Site Edinburgh, United Kingdom, EH4 2XRCompleted
United KingdomResearch Site Glasgow, United Kingdom, G12 0YNCompleted
United KingdomResearch Site Leeds, United Kingdom, LS9 7TFWithdrawn
United KingdomResearch Site Liverpool, United Kingdom, L69 3GAActive, not recruiting
United KingdomResearch Site London, United Kingdom, WC1E 6AGCompleted
United KingdomResearch Site London, United Kingdom, SE5 9RSCompleted
United KingdomResearch Site Manchester, United Kingdom, M20 4BXCompleted
United KingdomResearch Site Northwood, United Kingdom, HA6 2RNCompleted
United KingdomResearch Site Nottingham, United Kingdom, NG5 1PBCompleted
United KingdomResearch Site Surrey, United Kingdom, SM1 2DLActive, not recruiting
South KoreaResearch Site Seongnam-si, South Korea, 13620Completed
South KoreaResearch Site Seoul, South Korea, 03080Active, not recruiting
South KoreaResearch Site Seoul, South Korea, 6351Active, not recruiting
NetherlandsResearch Site Amsterdam, Netherlands, 1105 AZActive, not recruiting
NetherlandsResearch Site Maastricht, Netherlands, 6202 AZWithdrawn
United States of America , CAResearch Site Downey, CA, United States of America, 90241Withdrawn
United States of America , CAResearch Site La Jolla, CA, United States of America, 92093Withdrawn
United States of America , CAResearch Site Los Angeles, CA, United States of America, 90048Withdrawn
United States of America , CAResearch Site Los Angeles, CA, United States of America, 90030Withdrawn
United States of America , CAResearch Site Santa Monica, CA, United States of America, 90404Withdrawn
United States of America , CAResearch Site Stanford, CA, United States of America, 94305-5720Active, not recruiting
Canada , QCResearch Site Montreal, QC, Canada, H2X 3J4Withdrawn
Canada , QCResearch Site Sherbrooke, QC, Canada, J1G 2E8Completed
ItalyResearch Site Ancona, Italy, 60126Withdrawn
ItalyResearch Site Bologna, Italy, 40138Completed
ItalyResearch Site Milano, Italy, 20132Active, not recruiting
ItalyResearch Site Milano, Italy, 20133Completed
ItalyResearch Site Monserrato, Italy, 09042Withdrawn
ItalyResearch Site PADOVA, Italy, 35128Completed
ItalyResearch Site Parma, Italy, 43126Completed
ItalyResearch Site Pescara, Italy, 65100Completed
ItalyResearch Site Pisa, Italy, 56126Withdrawn
ItalyResearch Site Roma, Italy, 00144Active, not recruiting
ItalyResearch Site Roma, Italy, 00128Completed
ItalyResearch Site San Giovanni Rotondo, Italy, 71013Active, not recruiting
ItalyResearch Site Verona, Italy, 37134Active, not recruiting
United States of America , ILResearch Site Chicago, IL, United States of America, 60637Active, not recruiting
United States of America , ILResearch Site Evanston, IL, United States of America, 60201Withdrawn
United States of America , MDResearch Site Baltimore, MD, United States of America, 21287Active, not recruiting
United States of America , MDResearch Site Bethesda, MD, United States of America, 20889Withdrawn
United States of America , PAResearch Site Philadelphia, PA, United States of America, 19111Completed
United States of America , ConnecticutResearch Site New Haven, Connecticut, United States of America, 06510-3220Completed
United States of America , OHResearch Site Columbus, OH, United States of America, 43210Completed
United States of America , COResearch Site Aurora, CO, United States of America, 80045Completed
United States of America , FLResearch Site Boca Raton, FL, United States of America, 33486Active, not recruiting
United States of America , FLResearch Site Miami, FL, United States of America, 33136Withdrawn
United States of America , FLResearch Site Miami, FL, United States of America, 33136Active, not recruiting
United States of America , NYResearch Site Commack, NY, United States of America, 11725Completed
United States of America , NYResearch Site New York, NY, United States of America, 10032Completed
United States of America , NYResearch Site New York, NY, United States of America, 10022Active, not recruiting
United States of America , NYResearch Site New York, NY, United States of America, 10065Completed
United States of America , NYResearch Site Sleepy Hollow, NY, United States of America, 10591Withdrawn
United States of America , NYResearch Site West Harrison, NY, United States of America, 10604Withdrawn
United States of America , MOResearch Site St Louis, MO, United States of America, 63110Completed
United States of America , SCResearch Site Spartenburg, SC, United States of America, 29303Withdrawn
Canada , QuebecResearch Site Montreal, Quebec, Canada, H3T 1E2Completed
United States of America , ArizonaResearch Site Gilbert, Arizona, United States of America, 85234Completed
United States of America , CaliforniaResearch Site Orange, California, United States of America, 92868-3298Completed
United States of America , MAResearch Site Boston, MA, United States of America, 02114-2696Withdrawn
United States of America , MAResearch Site Boston, MA, United States of America, 02215Active, not recruiting
United States of America , WAResearch Site Seattle, WA, United States of America, 98109Withdrawn
United States of America , WAResearch Site Seattle, WA, United States of America, 98104Completed
Canada , MBResearch Site Winnipeg, MB, Canada, R2H 2A6Withdrawn
United States of America , TXResearch Site Arlington, TX, United States of America, 76012Withdrawn
United States of America , TXResearch Site Dallas, TX, United States of America, 75390Withdrawn
United States of America , TXResearch Site Houston, TX, United States of America, 77030Active, not recruiting
United States of America , New YorkResearch Site New York City, New York, United States of America, 10015Completed
United States of America , New YorkResearch Site Rockville Centre, New York, United States of America, 11570-1000Withdrawn
United States of America , NJResearch Site Basking Ridge, NJ, United States of America, 07920Withdrawn
United States of America , DCResearch Site Washington, DC, United States of America, 20007Withdrawn

Oversight


Is FDA regulated intervention: Yes 
Is IND/IDE protocol: Yes 
Section 801 trial: Yes 
Delayed Posting: No 
IND/IDE Grantor: CDER 
IND/IDE Number: 121412 
Has Expanded Access: No 

More Information


https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D081FC00001&attachmentIdentifier=9095e288-3d26-4c56-87dd-5dedc61f25c2&fileName=POLO_Revised_CSP_2-24Jul2019_Redacted.pdf&versionIdentifier=

Redacted_SAP

Publications:


Responsible Party:AstraZeneca
ClinicalTrials.gov Identifier:NCT02184195
Other Study ID Numbers:D081FC00001, 2014-001589-85
Health Authority:United States: Food and Drug Administration
Australia: National Health and Medical Research Council
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Canadian Institutes of Health Research
Israel: Israeli Health Ministry Pharmaceutical Administration
Spain: Spanish Agency of Medicines
Belgium: Federal Agency for Medicinal Products and Health Products
Korea: Food and Drug Administration

Keywords provided by AstraZeneca
BRCA, metastatic adenocarcinoma pancreas, maintenance olaparib monotherapy, first line platinum chemotherapy, pancreatic cancer, PARP inhibitor

Additional Relevant MeSH terms:
germline BRCA1/2 mutations andmetastatic adenocarcinoma of the pancreas

Participant Flow


Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study randomised patients at a total of 59 study centres in 12 countries: United States of America (13), Germany (8), France (7), Israel (7), Spain (7), United Kingdom (6), Italy (4), Belgium (2), Republic of Korea (2), Australia (1), Canada (1) and Netherlands (1).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening Part 1 was only required if a patient’s gBRCAm status was unknown and Screening Part 2 was for patients with known local germline BRCA (gBRCA) test. All other screening parameters were done as per the Study Schedule.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Participant Flow:   Overall Study

 Olaparib 300 mg twice daily (bd)Placebo
 STARTED 9262
 COMPLETED 4927
 NOT COMPLETED 4335
  Patient decision  31
  Eligibility criteria not fulfilled  01
  Death  4029
  Lost to Follow-up  02
  Other  02

Baseline Characteristics


Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

Description
Olaparib 300 mg twice daily (bd)
Placebo

Baseline Measures

 Olaparib 300 mg twice daily (bd)PlaceboTotal
Number of Participants
[units: Participants]
9262154
Age Continuous
[units: Years]
Mean ± Standard Deviation
58.2 ± 10.2756.4 ± 9.0757.5 ± 9.81
Sex: Female, Male
[units: Participants]
   
Female393170
Male533184
Race (NIH/OMB)
[units: Participants]
   
American Indian or Alaska Native101
Asian426
Native Hawaiian or Other Pacific Islander000
Black or African American505
White8259141
More than one race000
Unknown or Not Reported011
Ethnicity (NIH/OMB)
[units: Participants]
   
Hispanic or Latino426
Not Hispanic or Latino8860148
Unknown or Not Reported000

Outcome Measures


1. Primary Outcome Measure: Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)   [ Time Frame: Up to 4 years ]

Measure TypePrimary
Measure NameProgression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)
Measure DescriptionTo determine the efficacy of olaparib maintenance monotherapy compared to placebo by PFS. The PFS was defined as the time from randomisation until the date of objective radiological disease progression according to modified RECIST v1.1 or death (by any cause in the absence of disease progression) regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to disease progression.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)
[units: Months]
Median (95% Confidence Interval)
7.4 (4.14 to 11.01) 3.8 (3.52 to 4.86)

Statistical Analysis 1 for Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.0038
Hazard Ratio (HR)  [5] 0.531
95% Confidence Interval( 0.346 to 0.815 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

2. Secondary Outcome Measure: Overall Survival (OS)   [ Time Frame: Upto 4 years ]

Measure TypeSecondary
Measure NameOverall Survival (OS)
Measure DescriptionTo determine the efficacy by assessment of OS of olaparib maintenance monotherapy compared to placebo. The OS was defined as the time from the date of randomization until death due to any cause.
Time FrameUpto 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Overall Survival (OS)
[units: Months]
Median (95% Confidence Interval)
18.9 (14.85 to 26.15) 18.1 (12.62 to 26.12)

Statistical Analysis 1 for Overall Survival (OS)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.6833
Hazard Ratio (HR)  [5] 0.906
95% Confidence Interval( 0.563 to 1.457 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

3. Secondary Outcome Measure: Time from randomisation to second progression (PFS2)   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameTime from randomisation to second progression (PFS2)
Measure DescriptionTo determine efficacy by assessment of PFS2 of olaparib maintenance monotherapy compared to placebo. The PFS2 was defined as the time from the date of randomisation to the earliest of the progression event subsequent to that used for the primary variable PFS or death.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Time from randomisation to second progression (PFS2)
[units: Months]
Median (95% Confidence Interval)
13.2 (7.75 to 26.15) 9.2 (7.62 to 13.54)

Statistical Analysis 1 for Time from randomisation to second progression (PFS2)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.2597
Hazard Ratio (HR)  [5] 0.755
95% Confidence Interval( 0.464 to 1.230 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

4. Secondary Outcome Measure: Time from randomisation to second subsequent therapy or death (TSST)   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameTime from randomisation to second subsequent therapy or death (TSST)
Measure DescriptionTo determine the efficacy by assessment of TSST of olaparib maintenance monotherapy compared to placebo. The TSST was defined as time to second subsequent therapy or death.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Time from randomisation to second subsequent therapy or death (TSST)
[units: Months]
Median (95% Confidence Interval)
13.2 (8.84 to 20.04) 9.2 (8.34 to 13.14)

Statistical Analysis 1 for Time from randomisation to second subsequent therapy or death (TSST)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.0825
Hazard Ratio (HR)  [5] 0.678
95% Confidence Interval( 0.437 to 1.051 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

5. Secondary Outcome Measure: Time from randomisation to first subsequent therapy or death (TFST)   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameTime from randomisation to first subsequent therapy or death (TFST)
Measure DescriptionTo determine the efficacy by assessment of TFST of olaparib maintenance monotherapy compared to placebo. The TFST was defined as time to first subsequent therapy or death.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Time from randomisation to first subsequent therapy or death (TFST)
[units: Months]
Median (95% Confidence Interval)
8.6 (6.21 to 12.45) 5.7 (4.17 to 6.34)

Statistical Analysis 1 for Time from randomisation to first subsequent therapy or death (TFST)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.0013
Hazard Ratio (HR)  [5] 0.496
95% Confidence Interval( 0.324 to 0.760 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

6. Secondary Outcome Measure: Time from randomisation to study treatment discontinuation or death (TDT)   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameTime from randomisation to study treatment discontinuation or death (TDT)
Measure DescriptionTo determine the efficacy by assessment of TDT compared to placebo. compared to placebo. The TDT was defined as time to study treatment discontinuation or death.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Number of Full Analyisis Set Analyzed
Time from randomisation to study treatment discontinuation or death (TDT)
[units: Months]
Median (95% Confidence Interval)
7.2 (5.52 to 10.84) 3.8 (3.55 to 4.80)

Statistical Analysis 1 for Time from randomisation to study treatment discontinuation or death (TDT)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.0001
Hazard Ratio (HR)  [5] 0.446
95% Confidence Interval( 0.297 to 0.670 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

7. Secondary Outcome Measure: Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameNumber of participants with objective response rate (ORR) by BICR using modified RECIST 1.1
Measure DescriptionTo determine efficacy by assessment of objective response rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo. The ORR is defined as the number of with a BoR of CR and PR according to the BICR data divided by the number of patients in the treatment group with measurable disease at baseline.
Time FrameUp to 4 years
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients (patients with measurable disease at baseline).

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1
[units: Participants with response]
186

Statistical Analysis 1 for Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1

Groups  [1] All groups
Method  [3] Regression, Logistic
P-Value  [4] 0.1028
Odds Ratio (OR)  [5] 2.300
95% Confidence Interval( 0.886 to 6.761 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

8. Secondary Outcome Measure: Disease control rate (DCR) by BICR using modified RECIST 1.1   [ Time Frame: At 16 weeks ]

Measure TypeSecondary
Measure NameDisease control rate (DCR) by BICR using modified RECIST 1.1
Measure DescriptionEfficacy by assessment of disease control rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo.
Time FrameAt 16 weeks
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9262
Disease control rate (DCR) by BICR using modified RECIST 1.1
[units: Participants]
  
Yes4923
Yes4135
Yes24

No statistical analysis provided for Disease control rate (DCR) by BICR using modified RECIST 1.1

9. Secondary Outcome Measure: Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire   [ Time Frame: From baseline up to 6 months ]

Measure TypeSecondary
Measure NameAdjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire
Measure DescriptionTo assess the effect of olaparib on health-related quality of life (QoL) as measured by the EORTC-QLQ-C30 global QoL scale. The EORTC-QLQ-C30 is defined as EORTC QLQ-C30: a questionnaire (30 questions) used to evaluate disease symptoms, functional impacts (eg, physical functioning), and HRQoL and to characterize clinical benefit from the patient perspective. The HRQoL score ranges from 0 to 100. A higher score indicates better QoL. A score change of 10 points was pre-defined as clinically meaningful. bd twice daily.
Time FrameFrom baseline up to 6 months
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patient reported outcome (PRO) analysis set was defined as the analysis population for PRO data were a subset of the FAS (ITT) population who had evaluable baseline EORTC QLQ-C30 or QLQ-PAN26 forms where evaluable meant that at least 1 sub-scale baseline score could be determined from at least 1 of the 2 forms.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
8958
Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire
[units: Unit on scale]
Mean (95% Confidence Interval)
-1.20 (-4.014 to 1.618) 1.27 (-2.580 to 5.124)

Statistical Analysis 1 for Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire

Groups  [1] All groups
Method  [3] Mixed Models Analysis
P-Value  [4] 0.310
Mean Difference (Final Values)  [5] -2.47
95% Confidence Interval( -7.267 to 2.327 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5]  Other relevant estimation information:
  No text entered.

10. Secondary Outcome Measure: Number of participants with adverse events (AEs)   [ Time Frame: Up to 4 years ]

Measure TypeSecondary
Measure NameNumber of participants with adverse events (AEs)
Measure DescriptionTo assess the safety and tolerability of olaparib maintenance monotherapy. SAE: serious adverse events CTCAE: Common Terminology Criteria for Adverse Events
Time FrameUp to 4 years
Safety Issue?Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

 Olaparib 300 mg twice daily (bd)Placebo
Number of Participants Analyzed
[units:participants]
9160
Number of participants with adverse events (AEs)
[units: Participants]
  
Any AE8756
Any AE3614
Any AE00
Any AE229
Any AE51
Any AE323
Any AE152

No statistical analysis provided for Number of participants with adverse events (AEs)

Serious Adverse Events


Time FrameScreening to follow-up visit (30-day follow-up)
Additional DescriptionNo text entered.

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Serious Adverse Events

 Olaparib 300 mg twice daily (bd)Placebo
Total, serious adverse events   
# participants affected / at risk 22/91 (24.18%)9/60 (15.00%)
Infections and infestations  
Abdominal infection1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Infections and infestations  
Bartholinitis1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Infections and infestations  
Pneumonia1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Infections and infestations  
Urinary tract infection1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Blood and lymphatic system disorders  
Anaemia1  
# participants affected / at risk 6/91 (6.59%)0/60 (0.00%)
Blood and lymphatic system disorders  
Febrile Neutropenia1  
# participants affected / at risk 0/91 (0.00%)1/60 (1.67%)
Endocrine disorders  
Hypothyroidism1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Metabolism and nutrition disorders  
Decreased appetite1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Metabolism and nutrition disorders  
Hyperglycaemia1  
# participants affected / at risk 0/91 (0.00%)1/60 (1.67%)
Nervous system disorders  
Cerebrovascular accident1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Nervous system disorders  
Embolic stroke1  
# participants affected / at risk 0/91 (0.00%)1/60 (1.67%)
Nervous system disorders  
Transient ischaemic attack1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Cardiac disorders  
Cardiac failure1  
# participants affected / at risk 1/91 (1.10%)1/60 (1.67%)
Vascular disorders  
Vascular stenosis1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Respiratory, thoracic and mediastinal disorders  
Pleural effusion1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Respiratory, thoracic and mediastinal disorders  
Pneumothorax1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Abdominal pain1  
# participants affected / at risk 3/91 (3.30%)1/60 (1.67%)
Gastrointestinal disorders  
Constipation1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Duodenal perforation1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Gastric varices haemorrhage1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Incarcerated inguinal hernia1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Large intestinal obstruction1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Melaena1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Obstruction gastric1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Pancreatitis1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Gastrointestinal disorders  
Vomiting1  
# participants affected / at risk 1/91 (1.10%)3/60 (5.00%)
Hepatobiliary disorders  
Bile duct obstruction1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Hepatobiliary disorders  
Cholangitis1  
# participants affected / at risk 2/91 (2.20%)1/60 (1.67%)
Hepatobiliary disorders  
Cholecystitis1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
General disorders  
General physical health deterioration1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Investigations  
Platelet count decreased1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Injury, poisoning and procedural complications  
Anastomotic haemorrhage1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Product Issues  
Device occlusion1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
Product Issues  
Stent malfunction1  
# participants affected / at risk 1/91 (1.10%)0/60 (0.00%)
General disorders  
Pyrexia1  
# participants affected / at risk 0/91 (0.00%)2/60 (3.33%)
Events were collected by systematic assessment
1Term from vocabulary,  MedDRA version 21.1

Other Adverse Events


Time FrameScreening to follow-up visit (30-day follow-up)
Additional DescriptionNo text entered.

Frequency Threshold

Threshold above which other adverse events are reported 5%

Reporting Groups

 Description
Olaparib 300 mg twice daily (bd)Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
PlaceboRandomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Other Adverse Events

 Olaparib 300 mg twice daily (bd)Placebo
Total, other (not including serious) adverse events   
# participants affected / at risk 87/91 (95.60%)56/60 (93.33%)
Gastrointestinal disorders  
Nausea1  
# participants affected / at risk 41/91 (45.05%)14/60 (23.33%)
Gastrointestinal disorders  
Diarrhoea1  
# participants affected / at risk 26/91 (28.57%)9/60 (15.00%)
Gastrointestinal disorders  
Abdominal pain1  
# participants affected / at risk 23/91 (25.27%)14/60 (23.33%)
Gastrointestinal disorders  
Constipation1  
# participants affected / at risk 20/91 (21.98%)6/60 (10.00%)
Gastrointestinal disorders  
Vomiting1  
# participants affected / at risk 18/91 (19.78%)8/60 (13.33%)
Gastrointestinal disorders  
Stomatitis1  
# participants affected / at risk 7/91 (7.69%)3/60 (5.00%)
Gastrointestinal disorders  
Abdominal pain upper1  
# participants affected / at risk 6/91 (6.59%)8/60 (13.33%)
Gastrointestinal disorders  
Dry mouth1  
# participants affected / at risk 6/91 (6.59%)1/60 (1.67%)
Gastrointestinal disorders  
Dyspepsia1  
# participants affected / at risk 5/91 (5.49%)5/60 (8.33%)
Gastrointestinal disorders  
Abdominal distension1  
# participants affected / at risk 4/91 (4.40%)6/60 (10.00%)
Gastrointestinal disorders  
Flatulence1  
# participants affected / at risk 2/91 (2.20%)4/60 (6.67%)
General disorders  
Fatigue1  
# participants affected / at risk 41/91 (45.05%)16/60 (26.67%)
General disorders  
Asthenia1  
# participants affected / at risk 15/91 (16.48%)5/60 (8.33%)
General disorders  
Pyrexia1  
# participants affected / at risk 12/91 (13.19%)3/60 (5.00%)
General disorders  
Oedema peripheral1  
# participants affected / at risk 8/91 (8.79%)5/60 (8.33%)
Musculoskeletal and connective tissue disorders  
Back pain1  
# participants affected / at risk 17/91 (18.68%)10/60 (16.67%)
Musculoskeletal and connective tissue disorders  
Arthralgia1  
# participants affected / at risk 14/91 (15.38%)6/60 (10.00%)
Musculoskeletal and connective tissue disorders  
Muscle spasms1  
# participants affected / at risk 6/91 (6.59%)2/60 (3.33%)
Musculoskeletal and connective tissue disorders  
Pain in extremity1  
# participants affected / at risk 6/91 (6.59%)4/60 (6.67%)
Musculoskeletal and connective tissue disorders  
Musculoskeletal pain1  
# participants affected / at risk 5/91 (5.49%)3/60 (5.00%)
Musculoskeletal and connective tissue disorders  
Myalgia1  
# participants affected / at risk 5/91 (5.49%)3/60 (5.00%)
Musculoskeletal and connective tissue disorders  
Flank pain1  
# participants affected / at risk 1/91 (1.10%)4/60 (6.67%)
Nervous system disorders  
Dysgeusia1  
# participants affected / at risk 10/91 (10.99%)3/60 (5.00%)
Nervous system disorders  
Neuropathy peripheral1  
# participants affected / at risk 7/91 (7.69%)7/60 (11.67%)
Nervous system disorders  
Dizziness1  
# participants affected / at risk 6/91 (6.59%)3/60 (5.00%)
Nervous system disorders  
Headache1  
# participants affected / at risk 6/91 (6.59%)8/60 (13.33%)
Nervous system disorders  
Peripheral sensory neuropathy1  
# participants affected / at risk 6/91 (6.59%)2/60 (3.33%)
Blood and lymphatic system disorders  
Anaemia1  
# participants affected / at risk 23/91 (25.27%)10/60 (16.67%)
Blood and lymphatic system disorders  
Neutropenia1  
# participants affected / at risk 7/91 (7.69%)4/60 (6.67%)
Blood and lymphatic system disorders  
Thrombocytopenia1  
# participants affected / at risk 7/91 (7.69%)4/60 (6.67%)
Metabolism and nutrition disorders  
Decreased appetite1  
# participants affected / at risk 22/91 (24.18%)4/60 (6.67%)
Metabolism and nutrition disorders  
Hyperglycaemia1  
# participants affected / at risk 8/91 (8.79%)1/60 (1.67%)
Skin and subcutaneous tissue disorders  
Rash1  
# participants affected / at risk 11/91 (12.09%)2/60 (3.33%)
Skin and subcutaneous tissue disorders  
Pruritus1  
# participants affected / at risk 9/91 (9.89%)4/60 (6.67%)
Investigations  
Alanine aminotransferase increased1  
# participants affected / at risk 8/91 (8.79%)1/60 (1.67%)
Investigations  
Aspartate aminotransferase increased1  
# participants affected / at risk 6/91 (6.59%)1/60 (1.67%)
Investigations  
Blood creatinine increased1  
# participants affected / at risk 6/91 (6.59%)1/60 (1.67%)
Investigations  
Blood alkaline phosphatase increased1  
# participants affected / at risk 5/91 (5.49%)3/60 (5.00%)
Investigations  
Platelet count decreased1  
# participants affected / at risk 5/91 (5.49%)0/60 (0.00%)
Psychiatric disorders  
Insomnia1  
# participants affected / at risk 7/91 (7.69%)1/60 (1.67%)
Psychiatric disorders  
Anxiety1  
# participants affected / at risk 5/91 (5.49%)2/60 (3.33%)
Psychiatric disorders  
Depression1  
# participants affected / at risk 5/91 (5.49%)0/60 (0.00%)
Respiratory, thoracic and mediastinal disorders  
Dyspnoea1  
# participants affected / at risk 10/91 (10.99%)3/60 (5.00%)
Respiratory, thoracic and mediastinal disorders  
Cough1  
# participants affected / at risk 8/91 (8.79%)2/60 (3.33%)
Infections and infestations  
Nasopharyngitis1  
# participants affected / at risk 11/91 (12.09%)2/60 (3.33%)
Infections and infestations  
Influenza1  
# participants affected / at risk 5/91 (5.49%)0/60 (0.00%)
Events were collected by systematic assessment
1Term from vocabulary,  MedDRA version 21.1

Primary Outcome Measures:

  • Progression free survival (PFS) by central review of modified RECIST 1.1 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Efficacy by assessment of PFS (time from randomisation to objective disease progression according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) or death) of olaparib maintenance monotherapy compared to placebo, using blinded independent central review (BICR) of radiological scans.

Secondary Outcome Measures:

  • Overall survival (OS) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Efficacy by assessment of OS (time from randomisation to death by any cause) of olaparib maintenance monotherapy compared to placebo

  • Time from randomisation to second progression or death (PFS2) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Efficacy by assessment of PFS2 (time from randomisation to second progression, defined as objective radiological or symptomatic progression, or death) of olaparib maintenance monotherapy compared to placebo.

  • Time from randomisation to first subsequent therapy or death (TFST) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Efficacy by assessment of TFST (time from randomisation to the earlier of first subsequent therapy following study treatment discontinuation, or death) of olaparib maintenance monotherapy compared to placebo.

  • Time from randomisation to second subsequent therapy or death (TSST) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Efficacy by assessment of TSST (time from randomisation to the earlier of second subsequent therapy following study treatment discontinuation, or death) of olaparib maintenance monotherapy compared to placebo.

  • Time from randomisation to study treatment discontinuation or death (TDT) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Efficacy by assessment of TDT (time from randomisation to the earlier of study treatment discontinuation or death) of olaparib maintenance monotherapy compared to placebo. compared to placebo.

  • Objective response rate by BICR using modified RECIST 1.1 [ Time Frame: Up to 4 years. ] [ Designated as safety issue: No ]
    Efficacy by assessment of objective response rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo

  • Disease control rate by BICR using modified RECIST 1.1 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Efficacy by assessment of disease control rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo.

  • Adjusted mean change from baseline in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Assessment of the effect of olaparib on health-related quality of life (QoL) as measured by the EORTC-QLQ-C30 global QoL scale

  • Safety and tolerability of olaparib [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    Assessment of adverse events (AEs), physical examination, vital signs including blood pressure (BP), pulse, electrocardiogram (ECG) and laboratory findings including clinical chemistry and haematology.

  • Improvement rate of global quality of life (QoL) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Assessment of the effect of olaparib on improvement rate of global health status/QoL and pancreatic pain as measured by the EORTC-QLQ-C30 global QoL scale and the PAN-26 pancreatic pain scale.

Other Pre-specified Outcome Measures:

  • [ Time Frame:  ] [ Designated as safety issue:  ]

ArmsAssigned Interventions
Experimental: Olaparib
Olaparib tablets po. 300 mg twice daily
Drug: Olaparib
Tablet –100mg
Drug: Olaparib
Tablet-150mg
 
Placebo Comparator: Placebo
Placebo tablets twice daily
Drug: Placebo
Match Olaparib 100mg placebo
Drug: Placebo
Match Olaparib 150mg placebo
 

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:Global Clinical Leader
Organization:AstraZeneca AB
Phone1-877-240-9479 
E-mail:information.center@astrazeneca.com