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

Recruitment Status:
Completed

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 February 2023   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:Completed
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    [email protected]  
Contact Backup: AstraZeneca Cancer Study  Locator Service   1-877-400-4656    [email protected]  

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
BEResearch Site Antwerpen, BE, 2020Completed
BEResearch Site Brussel, BE, 1070Completed
BEResearch Site Leuven, BE, 3000Completed
CAResearch Site Toronto, CA, M5G 2M9Completed
DEResearch Site Berlin, DE, 10967Completed
DEResearch Site Berlin, DE, D-13353Completed
DEResearch Site Bochum, DE, 44791Completed
DEResearch Site Bonn, DE, 53127Completed
DEResearch Site Dresden, DE, 01307Completed
DEResearch Site Frankfurt am Main, DE, 60596Completed
DEResearch Site Hamburg, DE, 22291Completed
DEResearch Site Hamburg, DE, 20246Completed
DEResearch Site Hannover, DE, 30625Completed
DEResearch Site Leipzig, DE, 04103Completed
DEResearch Site München, DE, 81675Completed
DEResearch Site Schweinfurt, DE, 97422Completed
DEResearch Site Ulm, DE, 89081Completed
AUResearch Site Campbelltown, AU, 2560Completed
AUResearch Site Randwick, AU, 2031Completed
AUResearch Site St Leonards, AU, 2065Completed
CA , ONResearch Site London, ON, CA, N6A 4L6Completed
ILResearch Site Beer Sheva, IL, 84101Completed
ILResearch Site Haifa, IL, 3109601Completed
ILResearch Site Holon, IL, 58100Completed
ILResearch Site Nahariya, IL, 22100Completed
ILResearch Site Petah Tikva, IL, 4941492Active, not recruiting
ILResearch Site Ramat Gan, IL, 5265601Completed
ILResearch Site Rehovot, IL, 76100Completed
ILResearch Site Tel Aviv, IL, 6423906Completed
ILResearch Site Zefir, IL, 7030000Completed
ESResearch Site Barcelona, ES, 08035Completed
ESResearch Site Girona, ES, 17007Completed
ESResearch Site L'Hospitalet de Llobregat, ES, 08907Completed
ESResearch Site Madrid, ES, 28007Completed
ESResearch Site Madrid, ES, 28034Completed
ESResearch Site Madrid, ES, 28050Completed
ESResearch Site Madrid, ES, 28041Completed
ESResearch Site Málaga, ES, 29010Completed
ESResearch Site Pamplona, ES, 31008Completed
ESResearch Site Sabadell, ES, 8208Completed
ESResearch Site Santiago de Compostela, ES, 15706Completed
ESResearch Site Valencia, ES, 46009Completed
ESResearch Site Zaragoza, ES, 50009Completed
GBResearch Site Edinburgh, GB, EH4 2XRCompleted
GBResearch Site Glasgow, GB, G12 0YNCompleted
GBResearch Site Liverpool, GB, L69 3GACompleted
GBResearch Site London, GB, WC1E 6AGCompleted
GBResearch Site London, GB, SE5 9RSCompleted
GBResearch Site Manchester, GB, M20 4BXCompleted
GBResearch Site Northwood, GB, HA6 2RNCompleted
GBResearch Site Nottingham, GB, NG5 1PBCompleted
GBResearch Site Surrey, GB, SM1 2DLCompleted
FRResearch Site Amiens, FR, 80054Completed
FRResearch Site Besançon, FR, 25000Completed
FRResearch Site Bordeaux, FR, 33075Completed
FRResearch Site Brest Cedex, FR, 29609Completed
FRResearch Site Clichy Cedex, FR, 92118Completed
FRResearch Site La Roche sur Yon, FR, 85925Completed
FRResearch Site LILLE, FR, 59020Completed
FRResearch Site LYON CEDEX 03, FR, 69437Completed
FRResearch Site Nice, FR, 06189Completed
FRResearch Site PARIS, FR, 75014Completed
FRResearch Site Paris CEDEX 14, FR, 75674Completed
FRResearch Site POITIERS, FR, 86021Completed
FRResearch Site STRASBOURG Cedex, FR, 67065Completed
FRResearch Site Toulouse, FR, 31059Completed
FRResearch Site Villejuif, FR, 94800Completed
KRResearch Site Seongnam-si, KR, 13620Completed
KRResearch Site Seoul, KR, 03080Completed
KRResearch Site Seoul, KR, 6351Completed
US , CAResearch Site Orange, CA, US, 92868Completed
US , CAResearch Site Stanford, CA, US, 94305-5720Completed
ITResearch Site Bologna, IT, 40138Completed
ITResearch Site Milano, IT, 20132Completed
ITResearch Site Milano, IT, 20133Completed
ITResearch Site Padova, IT, 35128Completed
ITResearch Site Parma, IT, 43126Completed
ITResearch Site Pescara, IT, 65100Completed
ITResearch Site Roma, IT, 00144Completed
ITResearch Site Roma, IT, 00128Completed
ITResearch Site San Giovanni Rotondo, IT, 71013Completed
ITResearch Site Verona, IT, 37134Completed
US , ILResearch Site Chicago, IL, US, 60637Completed
US , MDResearch Site Baltimore, MD, US, 21287Completed
US , PAResearch Site Philadelphia, PA, US, 19111Completed
US , CTResearch Site New Haven, CT, US, 06510Completed
US , OHResearch Site Columbus, OH, US, 43210Completed
US , COResearch Site Aurora, CO, US, 80045Completed
US , FLResearch Site Boca Raton, FL, US, 33486Completed
US , FLResearch Site Miami, FL, US, 33136Completed
US , NYResearch Site Commack, NY, US, 11725Completed
US , NYResearch Site New York, NY, US, 10032Completed
US , NYResearch Site New York, NY, US, 10022Completed
US , NYResearch Site New York, NY, US, 10065Completed
US , NYResearch Site New York, NY, US, 10016Completed
US , MOResearch Site Saint Louis, MO, US, 63110Completed
CA , QuebecResearch Site Montreal, Quebec, CA, H3T 1E2Completed
US , AZResearch Site Gilbert, AZ, US, 85234Completed
NLResearch Site Amsterdam, NL, 1105 AZCompleted
CA , QCResearch Site Sherbrooke, QC, CA, J1G 2E8Completed
US , WAResearch Site Seattle, WA, US, 98104Completed
US , TXResearch Site Houston, TX, US, 77030Completed
US , MAResearch Site Boston, MA, US, 02215Completed

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 7355
 NOT COMPLETED 197
  Patients ongoing Study Treatment  197

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.
Full analysis set consisted of all randomised patients analysed on an intent to treat basis.

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.

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) 		19.0 (15.28 to 26.32) 19.2 (14.32 to 26.12)

Statistical Analysis 1 for Overall Survival (OS)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.3487
Hazard Ratio (HR)  [5] 0.831
95% Confidence Interval( 0.564 to 1.224 )
[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) 		16.9 (8.21 to 23.85) 9.3 (8.15 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] 0.0613
Hazard Ratio (HR)  [5] 0.659
95% Confidence Interval( 0.426 to 1.020 )
[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) 		14.9 (9.13 to 19.78) 9.6 (8.34 to 12.98)

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] 0.0111
Hazard Ratio (HR)  [5] 0.611
95% Confidence Interval( 0.418 to 0.894 )
[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) 		9.0 (6.21 to 12.85) 5.4 (3.94 to 6.21)

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] <0.0001
Hazard Ratio (HR)  [5] 0.442
95% Confidence Interval( 0.297 to 0.658 )
[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
Time from randomisation to study treatment discontinuation or death (TDT)
[units: Months]
Median (95% Confidence Interval) 		7.5 (5.52 to 10.97) 3.8 (3.61 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] 0.425
95% Confidence Interval( 0.289 to 0.627 )
[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.
All randomised 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]
7249
Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1
[units: Participants]
2211

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] 0.3273
Odds Ratio (OR)  [5] 1.520
95% Confidence Interval( 0.668 to 3.610 )
[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]
  
Yes5124
No3434
Not evaluable/missing74

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]
8455
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) 		-1.03 (-3.826 to 1.759) 1.18 (-2.585 to 4.939)

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] 0.355
Mean Difference (Final Values)  [5] -2.21
95% Confidence Interval( -6.371 to 2.496 )
[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.
Safety Analysis Set consisted of all patients who received at least one dose of study treatment.

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]
9061
Number of participants with adverse events (AEs)
[units: Participants]
  
Any AE8956
Any AE of CTCAE Grade 3 or higher4415
Any AE with outcome = death10
Any SAE (including events with outcome = death)2810
AnyAE leading to withdrawal of olaparib/placebo81
Any AE leading to dose interruption384
Any AE leading to dose reduction163

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

Serious Adverse Events

Time FrameFrom informed consent until 30 days after last dose + subsequent treatment-related events reported (maximum up to 4 years).
Additional DescriptionOnly 90 patients in Olaparib and 61 patients in Placebo group were reported for safety because 3 patients did not receive study treatment and were not reported in the safety table.

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 28/90 (31.11%)10/61 (16.39%)
Infections and infestations  
Abdominal infection1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Bartholinitis1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Pneumonia1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Urinary tract infection1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Blood and lymphatic system disorders  
Anaemia1  
# participants affected / at risk 7/90 (7.78%)0/61 (0.00%)
Blood and lymphatic system disorders  
Febrile Neutropenia1  
# participants affected / at risk 0/90 (0.00%)1/61 (1.64%)
Endocrine disorders  
Hypothyroidism1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Metabolism and nutrition disorders  
Decreased appetite1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Metabolism and nutrition disorders  
Hyperglycaemia1  
# participants affected / at risk 0/90 (0.00%)1/61 (1.64%)
Nervous system disorders  
Cerebrovascular accident1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Nervous system disorders  
Embolic stroke1  
# participants affected / at risk 0/90 (0.00%)1/61 (1.64%)
Nervous system disorders  
Transient ischaemic attack1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Cardiac disorders  
Cardiac failure1  
# participants affected / at risk 1/90 (1.11%)1/61 (1.64%)
Vascular disorders  
Vascular stenosis1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Respiratory, thoracic and mediastinal disorders  
Pleural effusion1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Respiratory, thoracic and mediastinal disorders  
Pneumothorax1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Abdominal pain1  
# participants affected / at risk 4/90 (4.44%)1/61 (1.64%)
Gastrointestinal disorders  
Constipation1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Duodenal perforation1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Gastric varices haemorrhage1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Incarcerated inguinal hernia1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Large intestinal obstruction1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Melaena1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Obstruction gastric1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Pancreatitis1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Vomiting1  
# participants affected / at risk 1/90 (1.11%)3/61 (4.92%)
Hepatobiliary disorders  
Bile duct obstruction1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Hepatobiliary disorders  
Cholangitis1  
# participants affected / at risk 2/90 (2.22%)1/61 (1.64%)
Hepatobiliary disorders  
Cholecystitis1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
General disorders  
General physical health deterioration1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Investigations  
Platelet count decreased1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Injury, poisoning and procedural complications  
Anastomotic haemorrhage1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Product Issues  
Device occlusion1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Product Issues  
Stent malfunction1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
General disorders  
Pyrexia1  
# participants affected / at risk 0/90 (0.00%)2/61 (3.28%)
Infections and infestations  
Bronchiolitis1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Empyema1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Pneumonia pneumococcal1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Influenza1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)  
Bladder papilloma1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Nervous system disorders  
Syncope1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Renal and urinary disorders  
Renal failure1  
# participants affected / at risk 0/90 (0.00%)1/61 (1.64%)
Injury, poisoning and procedural complications  
Incisional hernia1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Injury, poisoning and procedural complications  
Infusion related reaction1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Product Issues  
Device dislocation1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
†Events were collected by systematic assessment
1Term from vocabulary,  MedDRA version 21.1

Other Adverse Events

Time FrameFrom informed consent until 30 days after last dose + subsequent treatment-related events reported (maximum up to 4 years).
Additional DescriptionOnly 90 patients in Olaparib and 61 patients in Placebo group were reported for safety because 3 patients did not receive study treatment and were not reported in the safety table.

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 89/90 (98.89%)56/61 (91.80%)
Gastrointestinal disorders  
Nausea1  
# participants affected / at risk 44/90 (48.89%)15/61 (24.59%)
# events6617
Gastrointestinal disorders  
Diarrhoea1  
# participants affected / at risk 34/90 (37.78%)10/61 (16.39%)
# events4911
Gastrointestinal disorders  
Abdominal pain1  
# participants affected / at risk 26/90 (28.89%)15/61 (24.59%)
# events3917
Gastrointestinal disorders  
Constipation1  
# participants affected / at risk 25/90 (27.78%)7/61 (11.48%)
# events338
Gastrointestinal disorders  
Vomiting1  
# participants affected / at risk 23/90 (25.56%)9/61 (14.75%)
# events4912
Gastrointestinal disorders  
Stomatitis1  
# participants affected / at risk 8/90 (8.89%)3/61 (4.92%)
# events103
Gastrointestinal disorders  
Abdominal pain upper1  
# participants affected / at risk 9/90 (10.00%)9/61 (14.75%)
# events1110
Gastrointestinal disorders  
Dry mouth1  
# participants affected / at risk 8/90 (8.89%)1/61 (1.64%)
# events82
Gastrointestinal disorders  
Dyspepsia1  
# participants affected / at risk 9/90 (10.00%)5/61 (8.20%)
# events165
Gastrointestinal disorders  
Abdominal distension1  
# participants affected / at risk 5/90 (5.56%)6/61 (9.84%)
# events66
Gastrointestinal disorders  
Flatulence1  
# participants affected / at risk 2/90 (2.22%)4/61 (6.56%)
# events34
General disorders  
Fatigue1  
# participants affected / at risk 42/90 (46.67%)16/61 (26.23%)
# events4719
General disorders  
Asthenia1  
# participants affected / at risk 16/90 (17.78%)6/61 (9.84%)
# events246
General disorders  
Pyrexia1  
# participants affected / at risk 17/90 (18.89%)4/61 (6.56%)
# events285
General disorders  
Oedema peripheral1  
# participants affected / at risk 8/90 (8.89%)5/61 (8.20%)
# events115
Musculoskeletal and connective tissue disorders  
Back pain1  
# participants affected / at risk 24/90 (26.67%)13/61 (21.31%)
# events2813
Musculoskeletal and connective tissue disorders  
Arthralgia1  
# participants affected / at risk 19/90 (21.11%)11/61 (18.03%)
# events2511
Musculoskeletal and connective tissue disorders  
Muscle spasms1  
# participants affected / at risk 6/90 (6.67%)2/61 (3.28%)
# events92
Musculoskeletal and connective tissue disorders  
Pain in extremity1  
# participants affected / at risk 8/90 (8.89%)4/61 (6.56%)
# events104
Musculoskeletal and connective tissue disorders  
Myalgia1  
# participants affected / at risk 6/90 (6.67%)3/61 (4.92%)
# events65
Musculoskeletal and connective tissue disorders  
Flank pain1  
# participants affected / at risk 3/90 (3.33%)4/61 (6.56%)
# events34
Nervous system disorders  
Dysgeusia1  
# participants affected / at risk 6/90 (6.67%)3/61 (4.92%)
# events63
Nervous system disorders  
Neuropathy peripheral1  
# participants affected / at risk 9/90 (10.00%)7/61 (11.48%)
# events107
Nervous system disorders  
Dizziness1  
# participants affected / at risk 8/90 (8.89%)3/61 (4.92%)
# events84
Nervous system disorders  
Headache1  
# participants affected / at risk 8/90 (8.89%)8/61 (13.11%)
# events108
Nervous system disorders  
Peripheral sensory neuropathy1  
# participants affected / at risk 6/90 (6.67%)2/61 (3.28%)
# events62
Blood and lymphatic system disorders  
Anaemia1  
# participants affected / at risk 26/90 (28.89%)10/61 (16.39%)
# events3512
Blood and lymphatic system disorders  
Neutropenia1  
# participants affected / at risk 8/90 (8.89%)4/61 (6.56%)
# events94
Blood and lymphatic system disorders  
Thrombocytopenia1  
# participants affected / at risk 8/90 (8.89%)4/61 (6.56%)
# events94
Metabolism and nutrition disorders  
Decreased appetite1  
# participants affected / at risk 24/90 (26.67%)4/61 (6.56%)
# events295
Metabolism and nutrition disorders  
Hyperglycaemia1  
# participants affected / at risk 8/90 (8.89%)1/61 (1.64%)
# events151
Skin and subcutaneous tissue disorders  
Rash1  
# participants affected / at risk 12/90 (13.33%)3/61 (4.92%)
# events154
Skin and subcutaneous tissue disorders  
Pruritus1  
# participants affected / at risk 9/90 (10.00%)4/61 (6.56%)
# events114
Investigations  
Alanine aminotransferase increased1  
# participants affected / at risk 10/90 (11.11%)1/61 (1.64%)
# events161
Investigations  
Aspartate aminotransferase increased1  
# participants affected / at risk 8/90 (8.89%)1/61 (1.64%)
# events141
Investigations  
Blood creatinine increased1  
# participants affected / at risk 7/90 (7.78%)2/61 (3.28%)
# events122
Investigations  
Blood alkaline phosphatase increased1  
# participants affected / at risk 6/90 (6.67%)3/61 (4.92%)
# events73
Investigations  
Platelet count decreased1  
# participants affected / at risk 5/90 (5.56%)0/61 (0.00%)
# events90
Psychiatric disorders  
Insomnia1  
# participants affected / at risk 8/90 (8.89%)1/61 (1.64%)
# events81
Psychiatric disorders  
Anxiety1  
# participants affected / at risk 9/90 (10.00%)2/61 (3.28%)
# events102
Psychiatric disorders  
Depression1  
# participants affected / at risk 5/90 (5.56%)0/61 (0.00%)
# events60
Respiratory, thoracic and mediastinal disorders  
Dyspnoea1  
# participants affected / at risk 10/90 (11.11%)3/61 (4.92%)
# events114
Respiratory, thoracic and mediastinal disorders  
Cough1  
# participants affected / at risk 9/90 (10.00%)2/61 (3.28%)
# events133
Infections and infestations  
Nasopharyngitis1  
# participants affected / at risk 12/90 (13.33%)2/61 (3.28%)
# events212
Infections and infestations  
Influenza1  
# participants affected / at risk 6/90 (6.67%)0/61 (0.00%)
# events80
Gastrointestinal disorders  
Gastrooesophageal reflux disease1  
# participants affected / at risk 5/90 (5.56%)2/61 (3.28%)
# events52
General disorders  
Influenza like illness1  
# participants affected / at risk 6/90 (6.67%)0/61 (0.00%)
# events60
Nervous system disorders  
Paraesthesia1  
# participants affected / at risk 2/90 (2.22%)4/61 (6.56%)
# events34
Blood and lymphatic system disorders  
Lymphopenia1  
# participants affected / at risk 5/90 (5.56%)0/61 (0.00%)
# events90
Investigations  
Weight decreased1  
# participants affected / at risk 7/90 (7.78%)3/61 (4.92%)
# events73
Investigations  
Gamma-glutamyltransferase increased1  
# participants affected / at risk 6/90 (6.67%)1/61 (1.64%)
# events91
Investigations  
Neutrophil count decreased1  
# participants affected / at risk 6/90 (6.67%)0/61 (0.00%)
# events160
Vascular disorders  
Hypertension1  
# participants affected / at risk 5/90 (5.56%)3/61 (4.92%)
# events123
†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:[email protected]
.

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:Completed
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    [email protected]  
Contact Backup: AstraZeneca Cancer Study  Locator Service   1-877-400-4656    [email protected]  

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
BEResearch Site Antwerpen, BE, 2020Completed
BEResearch Site Brussel, BE, 1070Completed
BEResearch Site Leuven, BE, 3000Completed
CAResearch Site Toronto, CA, M5G 2M9Completed
DEResearch Site Berlin, DE, 10967Completed
DEResearch Site Berlin, DE, D-13353Completed
DEResearch Site Bochum, DE, 44791Completed
DEResearch Site Bonn, DE, 53127Completed
DEResearch Site Dresden, DE, 01307Completed
DEResearch Site Frankfurt am Main, DE, 60596Completed
DEResearch Site Hamburg, DE, 22291Completed
DEResearch Site Hamburg, DE, 20246Completed
DEResearch Site Hannover, DE, 30625Completed
DEResearch Site Leipzig, DE, 04103Completed
DEResearch Site München, DE, 81675Completed
DEResearch Site Schweinfurt, DE, 97422Completed
DEResearch Site Ulm, DE, 89081Completed
AUResearch Site Campbelltown, AU, 2560Completed
AUResearch Site Randwick, AU, 2031Completed
AUResearch Site St Leonards, AU, 2065Completed
CA , ONResearch Site London, ON, CA, N6A 4L6Completed
ILResearch Site Beer Sheva, IL, 84101Completed
ILResearch Site Haifa, IL, 3109601Completed
ILResearch Site Holon, IL, 58100Completed
ILResearch Site Nahariya, IL, 22100Completed
ILResearch Site Petah Tikva, IL, 4941492Active, not recruiting
ILResearch Site Ramat Gan, IL, 5265601Completed
ILResearch Site Rehovot, IL, 76100Completed
ILResearch Site Tel Aviv, IL, 6423906Completed
ILResearch Site Zefir, IL, 7030000Completed
ESResearch Site Barcelona, ES, 08035Completed
ESResearch Site Girona, ES, 17007Completed
ESResearch Site L'Hospitalet de Llobregat, ES, 08907Completed
ESResearch Site Madrid, ES, 28007Completed
ESResearch Site Madrid, ES, 28034Completed
ESResearch Site Madrid, ES, 28050Completed
ESResearch Site Madrid, ES, 28041Completed
ESResearch Site Málaga, ES, 29010Completed
ESResearch Site Pamplona, ES, 31008Completed
ESResearch Site Sabadell, ES, 8208Completed
ESResearch Site Santiago de Compostela, ES, 15706Completed
ESResearch Site Valencia, ES, 46009Completed
ESResearch Site Zaragoza, ES, 50009Completed
GBResearch Site Edinburgh, GB, EH4 2XRCompleted
GBResearch Site Glasgow, GB, G12 0YNCompleted
GBResearch Site Liverpool, GB, L69 3GACompleted
GBResearch Site London, GB, WC1E 6AGCompleted
GBResearch Site London, GB, SE5 9RSCompleted
GBResearch Site Manchester, GB, M20 4BXCompleted
GBResearch Site Northwood, GB, HA6 2RNCompleted
GBResearch Site Nottingham, GB, NG5 1PBCompleted
GBResearch Site Surrey, GB, SM1 2DLCompleted
FRResearch Site Amiens, FR, 80054Completed
FRResearch Site Besançon, FR, 25000Completed
FRResearch Site Bordeaux, FR, 33075Completed
FRResearch Site Brest Cedex, FR, 29609Completed
FRResearch Site Clichy Cedex, FR, 92118Completed
FRResearch Site La Roche sur Yon, FR, 85925Completed
FRResearch Site LILLE, FR, 59020Completed
FRResearch Site LYON CEDEX 03, FR, 69437Completed
FRResearch Site Nice, FR, 06189Completed
FRResearch Site PARIS, FR, 75014Completed
FRResearch Site Paris CEDEX 14, FR, 75674Completed
FRResearch Site POITIERS, FR, 86021Completed
FRResearch Site STRASBOURG Cedex, FR, 67065Completed
FRResearch Site Toulouse, FR, 31059Completed
FRResearch Site Villejuif, FR, 94800Completed
KRResearch Site Seongnam-si, KR, 13620Completed
KRResearch Site Seoul, KR, 03080Completed
KRResearch Site Seoul, KR, 6351Completed
US , CAResearch Site Orange, CA, US, 92868Completed
US , CAResearch Site Stanford, CA, US, 94305-5720Completed
ITResearch Site Bologna, IT, 40138Completed
ITResearch Site Milano, IT, 20132Completed
ITResearch Site Milano, IT, 20133Completed
ITResearch Site Padova, IT, 35128Completed
ITResearch Site Parma, IT, 43126Completed
ITResearch Site Pescara, IT, 65100Completed
ITResearch Site Roma, IT, 00144Completed
ITResearch Site Roma, IT, 00128Completed
ITResearch Site San Giovanni Rotondo, IT, 71013Completed
ITResearch Site Verona, IT, 37134Completed
US , ILResearch Site Chicago, IL, US, 60637Completed
US , MDResearch Site Baltimore, MD, US, 21287Completed
US , PAResearch Site Philadelphia, PA, US, 19111Completed
US , CTResearch Site New Haven, CT, US, 06510Completed
US , OHResearch Site Columbus, OH, US, 43210Completed
US , COResearch Site Aurora, CO, US, 80045Completed
US , FLResearch Site Boca Raton, FL, US, 33486Completed
US , FLResearch Site Miami, FL, US, 33136Completed
US , NYResearch Site Commack, NY, US, 11725Completed
US , NYResearch Site New York, NY, US, 10032Completed
US , NYResearch Site New York, NY, US, 10022Completed
US , NYResearch Site New York, NY, US, 10065Completed
US , NYResearch Site New York, NY, US, 10016Completed
US , MOResearch Site Saint Louis, MO, US, 63110Completed
CA , QuebecResearch Site Montreal, Quebec, CA, H3T 1E2Completed
US , AZResearch Site Gilbert, AZ, US, 85234Completed
NLResearch Site Amsterdam, NL, 1105 AZCompleted
CA , QCResearch Site Sherbrooke, QC, CA, J1G 2E8Completed
US , WAResearch Site Seattle, WA, US, 98104Completed
US , TXResearch Site Houston, TX, US, 77030Completed
US , MAResearch Site Boston, MA, US, 02215Completed

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

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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 7355
 NOT COMPLETED 197
  Patients ongoing Study Treatment  197

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.
Full analysis set consisted of all randomised patients analysed on an intent to treat basis.

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.

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:
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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) 		19.0 (15.28 to 26.32) 19.2 (14.32 to 26.12)

Statistical Analysis 1 for Overall Survival (OS)

Groups  [1] All groups
Method  [3] Other [Log-rank test]
P-Value  [4] 0.3487
Hazard Ratio (HR)  [5] 0.831
95% Confidence Interval( 0.564 to 1.224 )
[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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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) 		16.9 (8.21 to 23.85) 9.3 (8.15 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] 0.0613
Hazard Ratio (HR)  [5] 0.659
95% Confidence Interval( 0.426 to 1.020 )
[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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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) 		14.9 (9.13 to 19.78) 9.6 (8.34 to 12.98)

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] 0.0111
Hazard Ratio (HR)  [5] 0.611
95% Confidence Interval( 0.418 to 0.894 )
[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:
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[5]  Other relevant estimation information:
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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) 		9.0 (6.21 to 12.85) 5.4 (3.94 to 6.21)

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] <0.0001
Hazard Ratio (HR)  [5] 0.442
95% Confidence Interval( 0.297 to 0.658 )
[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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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
Time from randomisation to study treatment discontinuation or death (TDT)
[units: Months]
Median (95% Confidence Interval) 		7.5 (5.52 to 10.97) 3.8 (3.61 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] 0.425
95% Confidence Interval( 0.289 to 0.627 )
[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.
All randomised 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]
7249
Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1
[units: Participants]
2211

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] 0.3273
Odds Ratio (OR)  [5] 1.520
95% Confidence Interval( 0.668 to 3.610 )
[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]
  
Yes5124
No3434
Not evaluable/missing74

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]
8455
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) 		-1.03 (-3.826 to 1.759) 1.18 (-2.585 to 4.939)

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] 0.355
Mean Difference (Final Values)  [5] -2.21
95% Confidence Interval( -6.371 to 2.496 )
[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.
Safety Analysis Set consisted of all patients who received at least one dose of study treatment.

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]
9061
Number of participants with adverse events (AEs)
[units: Participants]
  
Any AE8956
Any AE of CTCAE Grade 3 or higher4415
Any AE with outcome = death10
Any SAE (including events with outcome = death)2810
AnyAE leading to withdrawal of olaparib/placebo81
Any AE leading to dose interruption384
Any AE leading to dose reduction163

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

Serious Adverse Events

Time FrameFrom informed consent until 30 days after last dose + subsequent treatment-related events reported (maximum up to 4 years).
Additional DescriptionOnly 90 patients in Olaparib and 61 patients in Placebo group were reported for safety because 3 patients did not receive study treatment and were not reported in the safety table.

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 28/90 (31.11%)10/61 (16.39%)
Infections and infestations  
Abdominal infection1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Bartholinitis1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Pneumonia1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Urinary tract infection1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Blood and lymphatic system disorders  
Anaemia1  
# participants affected / at risk 7/90 (7.78%)0/61 (0.00%)
Blood and lymphatic system disorders  
Febrile Neutropenia1  
# participants affected / at risk 0/90 (0.00%)1/61 (1.64%)
Endocrine disorders  
Hypothyroidism1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Metabolism and nutrition disorders  
Decreased appetite1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Metabolism and nutrition disorders  
Hyperglycaemia1  
# participants affected / at risk 0/90 (0.00%)1/61 (1.64%)
Nervous system disorders  
Cerebrovascular accident1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Nervous system disorders  
Embolic stroke1  
# participants affected / at risk 0/90 (0.00%)1/61 (1.64%)
Nervous system disorders  
Transient ischaemic attack1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Cardiac disorders  
Cardiac failure1  
# participants affected / at risk 1/90 (1.11%)1/61 (1.64%)
Vascular disorders  
Vascular stenosis1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Respiratory, thoracic and mediastinal disorders  
Pleural effusion1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Respiratory, thoracic and mediastinal disorders  
Pneumothorax1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Abdominal pain1  
# participants affected / at risk 4/90 (4.44%)1/61 (1.64%)
Gastrointestinal disorders  
Constipation1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Duodenal perforation1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Gastric varices haemorrhage1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Incarcerated inguinal hernia1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Large intestinal obstruction1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Melaena1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Obstruction gastric1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Pancreatitis1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Gastrointestinal disorders  
Vomiting1  
# participants affected / at risk 1/90 (1.11%)3/61 (4.92%)
Hepatobiliary disorders  
Bile duct obstruction1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Hepatobiliary disorders  
Cholangitis1  
# participants affected / at risk 2/90 (2.22%)1/61 (1.64%)
Hepatobiliary disorders  
Cholecystitis1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
General disorders  
General physical health deterioration1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Investigations  
Platelet count decreased1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Injury, poisoning and procedural complications  
Anastomotic haemorrhage1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Product Issues  
Device occlusion1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Product Issues  
Stent malfunction1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
General disorders  
Pyrexia1  
# participants affected / at risk 0/90 (0.00%)2/61 (3.28%)
Infections and infestations  
Bronchiolitis1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Empyema1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Pneumonia pneumococcal1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Infections and infestations  
Influenza1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)  
Bladder papilloma1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Nervous system disorders  
Syncope1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Renal and urinary disorders  
Renal failure1  
# participants affected / at risk 0/90 (0.00%)1/61 (1.64%)
Injury, poisoning and procedural complications  
Incisional hernia1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Injury, poisoning and procedural complications  
Infusion related reaction1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
Product Issues  
Device dislocation1  
# participants affected / at risk 1/90 (1.11%)0/61 (0.00%)
†Events were collected by systematic assessment
1Term from vocabulary,  MedDRA version 21.1

Other Adverse Events

Time FrameFrom informed consent until 30 days after last dose + subsequent treatment-related events reported (maximum up to 4 years).
Additional DescriptionOnly 90 patients in Olaparib and 61 patients in Placebo group were reported for safety because 3 patients did not receive study treatment and were not reported in the safety table.

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 89/90 (98.89%)56/61 (91.80%)
Gastrointestinal disorders  
Nausea1  
# participants affected / at risk 44/90 (48.89%)15/61 (24.59%)
# events6617
Gastrointestinal disorders  
Diarrhoea1  
# participants affected / at risk 34/90 (37.78%)10/61 (16.39%)
# events4911
Gastrointestinal disorders  
Abdominal pain1  
# participants affected / at risk 26/90 (28.89%)15/61 (24.59%)
# events3917
Gastrointestinal disorders  
Constipation1  
# participants affected / at risk 25/90 (27.78%)7/61 (11.48%)
# events338
Gastrointestinal disorders  
Vomiting1  
# participants affected / at risk 23/90 (25.56%)9/61 (14.75%)
# events4912
Gastrointestinal disorders  
Stomatitis1  
# participants affected / at risk 8/90 (8.89%)3/61 (4.92%)
# events103
Gastrointestinal disorders  
Abdominal pain upper1  
# participants affected / at risk 9/90 (10.00%)9/61 (14.75%)
# events1110
Gastrointestinal disorders  
Dry mouth1  
# participants affected / at risk 8/90 (8.89%)1/61 (1.64%)
# events82
Gastrointestinal disorders  
Dyspepsia1  
# participants affected / at risk 9/90 (10.00%)5/61 (8.20%)
# events165
Gastrointestinal disorders  
Abdominal distension1  
# participants affected / at risk 5/90 (5.56%)6/61 (9.84%)
# events66
Gastrointestinal disorders  
Flatulence1  
# participants affected / at risk 2/90 (2.22%)4/61 (6.56%)
# events34
General disorders  
Fatigue1  
# participants affected / at risk 42/90 (46.67%)16/61 (26.23%)
# events4719
General disorders  
Asthenia1  
# participants affected / at risk 16/90 (17.78%)6/61 (9.84%)
# events246
General disorders  
Pyrexia1  
# participants affected / at risk 17/90 (18.89%)4/61 (6.56%)
# events285
General disorders  
Oedema peripheral1  
# participants affected / at risk 8/90 (8.89%)5/61 (8.20%)
# events115
Musculoskeletal and connective tissue disorders  
Back pain1  
# participants affected / at risk 24/90 (26.67%)13/61 (21.31%)
# events2813
Musculoskeletal and connective tissue disorders  
Arthralgia1  
# participants affected / at risk 19/90 (21.11%)11/61 (18.03%)
# events2511
Musculoskeletal and connective tissue disorders  
Muscle spasms1  
# participants affected / at risk 6/90 (6.67%)2/61 (3.28%)
# events92
Musculoskeletal and connective tissue disorders  
Pain in extremity1  
# participants affected / at risk 8/90 (8.89%)4/61 (6.56%)
# events104
Musculoskeletal and connective tissue disorders  
Myalgia1  
# participants affected / at risk 6/90 (6.67%)3/61 (4.92%)
# events65
Musculoskeletal and connective tissue disorders  
Flank pain1  
# participants affected / at risk 3/90 (3.33%)4/61 (6.56%)
# events34
Nervous system disorders  
Dysgeusia1  
# participants affected / at risk 6/90 (6.67%)3/61 (4.92%)
# events63
Nervous system disorders  
Neuropathy peripheral1  
# participants affected / at risk 9/90 (10.00%)7/61 (11.48%)
# events107
Nervous system disorders  
Dizziness1  
# participants affected / at risk 8/90 (8.89%)3/61 (4.92%)
# events84
Nervous system disorders  
Headache1  
# participants affected / at risk 8/90 (8.89%)8/61 (13.11%)
# events108
Nervous system disorders  
Peripheral sensory neuropathy1  
# participants affected / at risk 6/90 (6.67%)2/61 (3.28%)
# events62
Blood and lymphatic system disorders  
Anaemia1  
# participants affected / at risk 26/90 (28.89%)10/61 (16.39%)
# events3512
Blood and lymphatic system disorders  
Neutropenia1  
# participants affected / at risk 8/90 (8.89%)4/61 (6.56%)
# events94
Blood and lymphatic system disorders  
Thrombocytopenia1  
# participants affected / at risk 8/90 (8.89%)4/61 (6.56%)
# events94
Metabolism and nutrition disorders  
Decreased appetite1  
# participants affected / at risk 24/90 (26.67%)4/61 (6.56%)
# events295
Metabolism and nutrition disorders  
Hyperglycaemia1  
# participants affected / at risk 8/90 (8.89%)1/61 (1.64%)
# events151
Skin and subcutaneous tissue disorders  
Rash1  
# participants affected / at risk 12/90 (13.33%)3/61 (4.92%)
# events154
Skin and subcutaneous tissue disorders  
Pruritus1  
# participants affected / at risk 9/90 (10.00%)4/61 (6.56%)
# events114
Investigations  
Alanine aminotransferase increased1  
# participants affected / at risk 10/90 (11.11%)1/61 (1.64%)
# events161
Investigations  
Aspartate aminotransferase increased1  
# participants affected / at risk 8/90 (8.89%)1/61 (1.64%)
# events141
Investigations  
Blood creatinine increased1  
# participants affected / at risk 7/90 (7.78%)2/61 (3.28%)
# events122
Investigations  
Blood alkaline phosphatase increased1  
# participants affected / at risk 6/90 (6.67%)3/61 (4.92%)
# events73
Investigations  
Platelet count decreased1  
# participants affected / at risk 5/90 (5.56%)0/61 (0.00%)
# events90
Psychiatric disorders  
Insomnia1  
# participants affected / at risk 8/90 (8.89%)1/61 (1.64%)
# events81
Psychiatric disorders  
Anxiety1  
# participants affected / at risk 9/90 (10.00%)2/61 (3.28%)
# events102
Psychiatric disorders  
Depression1  
# participants affected / at risk 5/90 (5.56%)0/61 (0.00%)
# events60
Respiratory, thoracic and mediastinal disorders  
Dyspnoea1  
# participants affected / at risk 10/90 (11.11%)3/61 (4.92%)
# events114
Respiratory, thoracic and mediastinal disorders  
Cough1  
# participants affected / at risk 9/90 (10.00%)2/61 (3.28%)
# events133
Infections and infestations  
Nasopharyngitis1  
# participants affected / at risk 12/90 (13.33%)2/61 (3.28%)
# events212
Infections and infestations  
Influenza1  
# participants affected / at risk 6/90 (6.67%)0/61 (0.00%)
# events80
Gastrointestinal disorders  
Gastrooesophageal reflux disease1  
# participants affected / at risk 5/90 (5.56%)2/61 (3.28%)
# events52
General disorders  
Influenza like illness1  
# participants affected / at risk 6/90 (6.67%)0/61 (0.00%)
# events60
Nervous system disorders  
Paraesthesia1  
# participants affected / at risk 2/90 (2.22%)4/61 (6.56%)
# events34
Blood and lymphatic system disorders  
Lymphopenia1  
# participants affected / at risk 5/90 (5.56%)0/61 (0.00%)
# events90
Investigations  
Weight decreased1  
# participants affected / at risk 7/90 (7.78%)3/61 (4.92%)
# events73
Investigations  
Gamma-glutamyltransferase increased1  
# participants affected / at risk 6/90 (6.67%)1/61 (1.64%)
# events91
Investigations  
Neutrophil count decreased1  
# participants affected / at risk 6/90 (6.67%)0/61 (0.00%)
# events160
Vascular disorders  
Hypertension1  
# participants affected / at risk 5/90 (5.56%)3/61 (4.92%)
# events123
†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:[email protected]