Phase II umbrella study of novel anti-cancer agents in patients with NSCLC who progressed on an anti-PD-1/PD-L1 containing therapy  (HUDSON)

Recruitment Status:
Recruiting

Sponsor:
AstraZeneca

Information Provided by (Responsible Party):
AstraZeneca

ClinicalTrials.gov Identifier:
NCT03334617

Verification:
Verified 01 May 2022   by AstraZeneca

History of Changes:
ClinicalTrials.gov

Purpose

This is an open-label, multi-centre, umbrella Phase II study in patients with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms.

Official Title:An Open-Label, Multi-Drug, Biomarker-Directed, Multi-Centre Phase II Umbrella Study in Patients with Non-Small Cell Lung Cancer, who Progressed on an anti-PD-1/PD-L1 Containing Therapy (HUDSON).
Study Type:Interventional
Overall Recruitment Status:Recruiting
Study Start Date:18 December 2017
Study Start Date Type:Actual
Primary Completion Date:02 January 2026
Study Design: Allocation: Non-randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Model Description: This is an open-label, multi-centre, umbrella Phase II study in patients with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms. Within each module, there will be treatment cohorts.
ConditionInterventionPhase
Non-Small Cell Lung Cancer
Drug: Durvalumab
Drug: AZD9150
Drug: AZD6738
Drug: Vistusertib
Drug: Olaparib
Drug: Oleclumab
Drug: trastuzumab deruxtecan
Drug: cediranib
Drug: AZD6738 (ceralasertib)
Drug: AZD6738 (ceralasertib)
Drug: AZD6738 (ceralasertib) (240 mg or 160 mg)
Phase 2
Ages Eligible for Study: 18 Years  to 99 Years
Genders Eligible for Study: Both
Gender Based: No
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

- At least 18 years of age at the time of signing the informed consent form.

- Patient must have histologically or cytologically confirmed metastatic or locally advanced and recurrent NSCLC which is progressing.

- Patients eligible for second- or later-line therapy, who must have received an antiPD1/PD-L1 containing therapy and a platinum-doublet regimen for locally advanced or metastatic NSCLC either separately or in combination. Prior durvalumab is acceptable. The patient must have had disease progression on a prior line of antiPD1/PD-L1 therapy.

- ECOG/WHO performance status of 0 to 1, and a minimum life expectancy of 12 weeks.

- Patient must have at least 1 lesion that can be accurately measured. A previously irradiated lesion can be considered a target lesion if the lesion has clearly progressed.

- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.


Exclusion Criteria:

- Patients whose tumour samples have targetable alterations in EGFR and/or ALK are excluded. In addition, patients whose tumour samples are known to have targetable alterations in ROS1, BRAF, MET or RET, are to be excluded.

- Active or prior documented autoimmune or inflammatory disorders.

- Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).

- Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control.

- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients, or history of severe hypersensitivity reactions to other monoclonal antibodies.

- Patient has spinal cord compression or symptomatic brain metastases.

- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Patients may receive treatment with bisphosphonates or receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitors for the treatment of bone metastases.

-history of active primary immunodeficiency


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    [email protected]  

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator: John  Heymach , M.D, Ph.D   The University of Texas MD Anderson Cancer Center

Locations

CountryLocationFacilityContactStatus
ATResearch Site Innsbruck, AT, 6020Recruiting
ATResearch Site Salzburg, AT, 5020Recruiting
ATResearch Site Wien, AT, 1210Recruiting
ATResearch Site Wien, AT, 1140Recruiting
CA , ONResearch Site Brampton, ON, CA, L2P 2V3Recruiting
CA , ONResearch Site Ottawa, ON, CA, K1H 8L6Recruiting
CA , ONResearch Site Toronto, ON, CA, M5G 2M9Recruiting
KRResearch Site Seoul, KR, 135-710Recruiting
KRResearch Site Seoul, KR, 03080Recruiting
KRResearch Site Seoul, KR, 05505Recruiting
CA , ABResearch Site Edmonton, AB, CA, T6G 1Z2Recruiting
CA , QCResearch Site Montreal, QC, CA, H2X 3E4Recruiting
US , MDResearch Site Baltimore, MD, US, 21224Recruiting
US , MDResearch Site Baltimore, MD, US, 21287Recruiting
US , CAResearch Site Duarte, CA, US, 91010Recruiting
US , CAResearch Site Fullerton, CA, US, 92835Recruiting
US , CAResearch Site La Jolla, CA, US, 92093Recruiting
US , CAResearch Site Los Angeles, CA, US, 90095Recruiting
US , MOResearch Site Saint Louis, MO, US, 63110Recruiting
US , MAResearch Site Boston, MA, US, 02215Recruiting
US , MAResearch Site Boston, MA, US, 02215Terminated
US , MAResearch Site Boston, MA, US, 02114Withdrawn
US , PAResearch Site Philadelphia, PA, US, 19111Recruiting
US , PAResearch Site Pittsburgh, PA, US, 15232Recruiting
US , TNResearch Site Nashville, TN, US, 37203Recruiting
US , TNResearch Site Nashville, TN, US, 37212Terminated
ILResearch Site Haifa, IL, 31096Completed
ILResearch Site Kfar Saba, IL, 95847Active, not recruiting
ILResearch Site Petah Tikva, IL, 49100Active, not recruiting
ILResearch Site Ramat Gan, IL, 5265601Active, not recruiting
US , NYResearch Site New York, NY, US, 10032Recruiting
FRResearch Site Bordeaux, FR, 33076Recruiting
FRResearch Site Nantes Cedex 1, FR, 44093Recruiting
FRResearch Site Paris, FR, 75877Recruiting
FRResearch Site Pierre Benite, FR, 69310Withdrawn
FRResearch Site Villejuif, FR, 94800Recruiting
US , TXResearch Site Houston, TX, US, 77030Recruiting
US , DCResearch Site Washington, DC, US, 20016Recruiting
US , VAResearch Site Fairfax, VA, US, 22031Recruiting
US , MNResearch Site Minneapolis, MN, US, 55455Withdrawn
US , ILResearch Site Chicago, IL, US, 60637Recruiting
DEResearch Site Berlin, DE, 12203Recruiting
DEResearch Site Essen, DE, 45122Withdrawn
DEResearch Site Esslingen a.N., DE, 73730Recruiting
DEResearch Site Frankfurt, DE, 60590Withdrawn
DEResearch Site Großhansdorf, DE, 22927Recruiting
DEResearch Site Halle, DE, 06120Withdrawn
DEResearch Site Heidelberg, DE, 69126Recruiting
DEResearch Site Köln, DE, 50924Terminated
DEResearch Site Würzburg, DE, 97078Withdrawn
ESResearch Site Barcelona, ES, 08036Recruiting
ESResearch Site Madrid, ES, 28034Recruiting
ESResearch Site Madrid, ES, 28007Recruiting
ESResearch Site Sevilla, ES, 41009Recruiting
US , FLResearch Site Tampa, FL, US, 33612Withdrawn
US , MIResearch Site Detroit, MI, US, 48201Withdrawn

No attachments posted.

.

Purpose

This is an open-label, multi-centre, umbrella Phase II study in patients with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms.

Official Title:An Open-Label, Multi-Drug, Biomarker-Directed, Multi-Centre Phase II Umbrella Study in Patients with Non-Small Cell Lung Cancer, who Progressed on an anti-PD-1/PD-L1 Containing Therapy (HUDSON).
Study Type:Interventional
Overall Recruitment Status:Recruiting
Study Start Date:18 December 2017
Study Start Date Type:Actual
Primary Completion Date:02 January 2026
Study Design: Allocation: Non-randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Model Description: This is an open-label, multi-centre, umbrella Phase II study in patients with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms. Within each module, there will be treatment cohorts.
ConditionInterventionPhase
Non-Small Cell Lung Cancer
Drug: Durvalumab
Drug: AZD9150
Drug: AZD6738
Drug: Vistusertib
Drug: Olaparib
Drug: Oleclumab
Drug: trastuzumab deruxtecan
Drug: cediranib
Drug: AZD6738 (ceralasertib)
Drug: AZD6738 (ceralasertib)
Drug: AZD6738 (ceralasertib) (240 mg or 160 mg)
Phase 2
Ages Eligible for Study: 18 Years  to 99 Years
Genders Eligible for Study: Both
Gender Based: No
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

- At least 18 years of age at the time of signing the informed consent form.

- Patient must have histologically or cytologically confirmed metastatic or locally advanced and recurrent NSCLC which is progressing.

- Patients eligible for second- or later-line therapy, who must have received an antiPD1/PD-L1 containing therapy and a platinum-doublet regimen for locally advanced or metastatic NSCLC either separately or in combination. Prior durvalumab is acceptable. The patient must have had disease progression on a prior line of antiPD1/PD-L1 therapy.

- ECOG/WHO performance status of 0 to 1, and a minimum life expectancy of 12 weeks.

- Patient must have at least 1 lesion that can be accurately measured. A previously irradiated lesion can be considered a target lesion if the lesion has clearly progressed.

- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.


Exclusion Criteria:

- Patients whose tumour samples have targetable alterations in EGFR and/or ALK are excluded. In addition, patients whose tumour samples are known to have targetable alterations in ROS1, BRAF, MET or RET, are to be excluded.

- Active or prior documented autoimmune or inflammatory disorders.

- Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).

- Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control.

- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients, or history of severe hypersensitivity reactions to other monoclonal antibodies.

- Patient has spinal cord compression or symptomatic brain metastases.

- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Patients may receive treatment with bisphosphonates or receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitors for the treatment of bone metastases.

-history of active primary immunodeficiency


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    [email protected]  

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator: John  Heymach , M.D, Ph.D   The University of Texas MD Anderson Cancer Center

Locations

CountryLocationFacilityContactStatus
ATResearch Site Innsbruck, AT, 6020Recruiting
ATResearch Site Salzburg, AT, 5020Recruiting
ATResearch Site Wien, AT, 1210Recruiting
ATResearch Site Wien, AT, 1140Recruiting
CA , ONResearch Site Brampton, ON, CA, L2P 2V3Recruiting
CA , ONResearch Site Ottawa, ON, CA, K1H 8L6Recruiting
CA , ONResearch Site Toronto, ON, CA, M5G 2M9Recruiting
KRResearch Site Seoul, KR, 135-710Recruiting
KRResearch Site Seoul, KR, 03080Recruiting
KRResearch Site Seoul, KR, 05505Recruiting
CA , ABResearch Site Edmonton, AB, CA, T6G 1Z2Recruiting
CA , QCResearch Site Montreal, QC, CA, H2X 3E4Recruiting
US , MDResearch Site Baltimore, MD, US, 21224Recruiting
US , MDResearch Site Baltimore, MD, US, 21287Recruiting
US , CAResearch Site Duarte, CA, US, 91010Recruiting
US , CAResearch Site Fullerton, CA, US, 92835Recruiting
US , CAResearch Site La Jolla, CA, US, 92093Recruiting
US , CAResearch Site Los Angeles, CA, US, 90095Recruiting
US , MOResearch Site Saint Louis, MO, US, 63110Recruiting
US , MAResearch Site Boston, MA, US, 02215Recruiting
US , MAResearch Site Boston, MA, US, 02215Terminated
US , MAResearch Site Boston, MA, US, 02114Withdrawn
US , PAResearch Site Philadelphia, PA, US, 19111Recruiting
US , PAResearch Site Pittsburgh, PA, US, 15232Recruiting
US , TNResearch Site Nashville, TN, US, 37203Recruiting
US , TNResearch Site Nashville, TN, US, 37212Terminated
ILResearch Site Haifa, IL, 31096Completed
ILResearch Site Kfar Saba, IL, 95847Active, not recruiting
ILResearch Site Petah Tikva, IL, 49100Active, not recruiting
ILResearch Site Ramat Gan, IL, 5265601Active, not recruiting
US , NYResearch Site New York, NY, US, 10032Recruiting
FRResearch Site Bordeaux, FR, 33076Recruiting
FRResearch Site Nantes Cedex 1, FR, 44093Recruiting
FRResearch Site Paris, FR, 75877Recruiting
FRResearch Site Pierre Benite, FR, 69310Withdrawn
FRResearch Site Villejuif, FR, 94800Recruiting
US , TXResearch Site Houston, TX, US, 77030Recruiting
US , DCResearch Site Washington, DC, US, 20016Recruiting
US , VAResearch Site Fairfax, VA, US, 22031Recruiting
US , MNResearch Site Minneapolis, MN, US, 55455Withdrawn
US , ILResearch Site Chicago, IL, US, 60637Recruiting
DEResearch Site Berlin, DE, 12203Recruiting
DEResearch Site Essen, DE, 45122Withdrawn
DEResearch Site Esslingen a.N., DE, 73730Recruiting
DEResearch Site Frankfurt, DE, 60590Withdrawn
DEResearch Site Großhansdorf, DE, 22927Recruiting
DEResearch Site Halle, DE, 06120Withdrawn
DEResearch Site Heidelberg, DE, 69126Recruiting
DEResearch Site Köln, DE, 50924Terminated
DEResearch Site Würzburg, DE, 97078Withdrawn
ESResearch Site Barcelona, ES, 08036Recruiting
ESResearch Site Madrid, ES, 28034Recruiting
ESResearch Site Madrid, ES, 28007Recruiting
ESResearch Site Sevilla, ES, 41009Recruiting
US , FLResearch Site Tampa, FL, US, 33612Withdrawn
US , MIResearch Site Detroit, MI, US, 48201Withdrawn

Oversight


Is IND/IDE protocol: Yes 
IND/IDE Grantor: CDER 
IND/IDE Number: 138050 
Has Expanded Access: No 
U.S. FDA-regulated Drug: Yes 
U.S. FDA-regulated Device: No 
Product Exported From U.S.: No 

More Information


No publications provided

Responsible Party:AstraZeneca
ClinicalTrials.gov Identifier:NCT03334617
Other Study ID Numbers:D6185C00001, 2017-002208-28, 138050 [Registry Identifier : IND]

Keywords provided by AstraZeneca
Non-small cell lung cancer
NSCLC
anti-PD-1/PD-L1
umbrella study
Durvalumab
MEDI4736
Olaparib
AZD2281
AZD9150
AZD6738
Vistusertib
AZD2014
Oleclumab
MEDI9447
Trastuzumab deruxtecan
DS-8201a
cediranib
AZD2171

Additional Relevant MeSH terms:
Non-Small Cell Lung Cancer

Primary Outcome Measures:

  • Assessment of the efficacy of each treatment by evaluation of objective response rate [ Time Frame: 12 weeks ] [ Designated as safety issue:  ]
    Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

    Objective response rate (ORR)

Secondary Outcome Measures:

  • Disease control rate (DCR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, up to 3.5 years. ] [ Designated as safety issue:  ]
    Assessment of the anti-tumour activity of each therapy.

  • Best percentage change in tumour size using RECIST 1.1 assessment for the anti-tumour activity of each therapy [ Time Frame: Through to study completion, up to 3.5 years. ] [ Designated as safety issue:  ]
    Assessment of the anti-tumour activity of each therapy.

  • Duration of response (DoR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, up to 3.5 years ] [ Designated as safety issue:  ]
    Assessment of the anti-tumour activity of each therapy.

  • Progression free survival (PFS) using RECIST 1.1 assessment for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, up to 3.5 years. ] [ Designated as safety issue:  ]
    Assessment of the anti-tumour activity of each therapy.

  • Overall surival (OS) [ Time Frame: Through to study completion, up to 4.5 years. ] [ Designated as safety issue:  ]
    Assessment of the anti-tumour activity of each therapy.

Other Pre-specified Outcome Measures:

  • Incidence of adverse events/serious adverse events to assess the safety and tolerability of each treatment [ Time Frame: Through to study completion, up to 3.5 years. ] [ Designated as safety issue:  ]
    Physical examinations, laboratory findings, and vital signs
    AEs/SAEs collected throughout the study, from informed consent until the safety follow-up visit

ArmsAssigned Interventions
Experimental: Durvalumab + olaparib
Durvalumab given in combination with olaparib .
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days
Drug: Olaparib
Olaparib (AZD2281) given orally at 300 mg BD
 
Experimental: Durvalumab + AZD9150
Durvalumab given in combination with AZD9150.
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days
Drug: AZD9150
AZD9150 given IV at 200mg every other day of a 1-week lead-in period followed by QW
 
Experimental: Durvalumab + AZD6738
Durvalumab given in combination with AZD6738.
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days
Drug: AZD6738
AZD6738 given orally at 240mg twice daily in Cycle 0 Days 1-7, followed by 7 days on treatment in each cycle between Days 22-28
 
Experimental: Durvalumab + vistusertib
Durvalumab given in combination with Vistusertib (AZD2014).
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days
Drug: Vistusertib
Vistusertib (AZD2014) given orally at a dose of 125 mg BD on an intermittent dosing schedule of 2 days on, 5 days off
 
Experimental: Durvalumab + Oleclumab
Durvalumab given in combination with Oleclumab
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days
Drug: Oleclumab
Oleclumab given at dose level 1 for 2 cycles and then dose level 2 thereafter
 
Experimental: durvalumab + trastuzumab deruxtecan
durvalumab given in combination with trastuzumab deruxtecan (DS-8201a)
Drug: trastuzumab deruxtecan
Durvalumab given IV at 1120mg Q3W ±2 days for Module 6 only &
trastuzumab deruxtecan given at 5.4 mg/kg via IV infusion Q3W ±2 days
 
Experimental: durvalumab + cediranib
durvalumab given in combination with cediranib (AZD2171)
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days
Drug: cediranib
cediranib given orally at 20 mg tablets on an intermittent schedule
(5 days on, 2 days off), starting on C1D1
 
Experimental: AZD6738 (ceralasertib) monotherapy
AZD6738 (ceralasertib) given as monotherapy
Drug: AZD6738 (ceralasertib)
AZD6738 given at 240 mg twice daily for 14 days on treatment in each 28-day cycle, between Days 1 and 14.
 
Experimental: durvalumab & AZD6738 (ceralasertib)
durvalumab given in combination with AZD6738 (D15-D28)
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days
Drug: AZD6738 (ceralasertib)
AZD6738 given orally at 240mg twice daily for 14 days in each 28 day cycle (starting from Cycle 1) between Days 15-28
 
Experimental: durvalumab & AZD6738 (ceralasertib) (240 mg or 160 mg)
durvalumab in combination with twice daily 160 mg or 240 mg AZD6738 (D22-D28)
Drug: AZD6738 (ceralasertib) (240 mg or 160 mg)
AZD6738 given orally at 240mg or 160mg twice daily in Cycle 0 Days 1-7, followed by 7 days on treatment in each cycle between Days 22-28