Ignite Creation Date:
2025-12-24 @ 7:59 PM
Ignite Modification Date:
2026-01-10 @ 3:40 PM
Study NCT ID:
NCT02484404
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-11-25
First Post:
2015-06-25
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase I/II Study of the Anti-Programmed Death Ligand-1 Durvalumab Antibody (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Can...
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase I/II Study of the Anti-Programmed Death Ligand-1 Antibody Durvalumab (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Cancers
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-11-21
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
\- Durvalumab is a drug that may help people s immune systems respond to and kill cancer cells. Olaparib is a drug that may inhibit repairing DNA damage of cancer cells. Cediranib is a drug that may stop the blood vessel growth of cancer cells. This study has two components. In the phase 1 component of the study, researchers want to investigate how well participants tolerate the combination of these drugs in treating advanced solid tumors, and in the phase 2 part of this study, researchers want to study if the combination treatments are effective in ovarian cancer.
Objectives:
\- Phase 2 part of the study: To determine how effective this combination is in treating ovarian cancer.
Eligibility:
\- Phase 2 part of the study: Adults age 18 or older with advanced or recurrent ovarian cancer that has no standard treatment.
Design:
* Participants will be screened with medical history, physical exam, and blood and urine tests. They will have CT or MRI scans. For these, they will lie in a machine that takes pictures of their bodies.
* Phase 2 part of the study requests the participants to have tumor samples removed.
* Participants will get Durvalumab through an IV. A small plastic tube will be inserted into a vein. The drug will be given every 4 weeks until disease progression.
* Participants will take olaparib or cediranib by mouth every day.
* Every 28 days will be 1 cycle. For cycle 1, participants will have 2 study visits. All other cycles, they will have 1 visit. At these visits, they will repeat the screening procedures.
* Patients will keep a drug and diarrhea diary.
* Patients on cediranib will monitor their blood pressure and keep a blood pressure diary.
* Participants who can become pregnant, or have a partner who can become pregnant, must practice an effective form of birth control.
* After 12 cycles, participants will have 1-3 months of follow-up.
\- Durvalumab is a drug that may help people s immune systems respond to and kill cancer cells. Olaparib is a drug that may inhibit repairing DNA damage of cancer cells. Cediranib is a drug that may stop the blood vessel growth of cancer cells. This study has two components. In the phase 1 component of the study, researchers want to investigate how well participants tolerate the combination of these drugs in treating advanced solid tumors, and in the phase 2 part of this study, researchers want to study if the combination treatments are effective in ovarian cancer.
Objectives:
\- Phase 2 part of the study: To determine how effective this combination is in treating ovarian cancer.
Eligibility:
\- Phase 2 part of the study: Adults age 18 or older with advanced or recurrent ovarian cancer that has no standard treatment.
Design:
* Participants will be screened with medical history, physical exam, and blood and urine tests. They will have CT or MRI scans. For these, they will lie in a machine that takes pictures of their bodies.
* Phase 2 part of the study requests the participants to have tumor samples removed.
* Participants will get Durvalumab through an IV. A small plastic tube will be inserted into a vein. The drug will be given every 4 weeks until disease progression.
* Participants will take olaparib or cediranib by mouth every day.
* Every 28 days will be 1 cycle. For cycle 1, participants will have 2 study visits. All other cycles, they will have 1 visit. At these visits, they will repeat the screening procedures.
* Patients will keep a drug and diarrhea diary.
* Patients on cediranib will monitor their blood pressure and keep a blood pressure diary.
* Participants who can become pregnant, or have a partner who can become pregnant, must practice an effective form of birth control.
* After 12 cycles, participants will have 1-3 months of follow-up.
Detailed Description:
Background:
Disruption of the immune checkpoint PD-1/PD-L1 pathway yielded clinical activity in subsets of advanced solid tumors, such as melanoma and lung cancer.
Olaparib (O), a PARP inhibitor (PARPi), has demonstrated single agent activity in recurrent ovarian cancer (OvCa), and subsets of prostate, triple negative breast or lung cancers.
Our recent randomized phase 2 study showed that O and cediranib (C), a VEGFR1-3 inhibitor was clinically superior to O alone in platinum-sensitive recurrent OvCa.
We hypothesize that increased DNA damage by PARP inhibition and/or reduced angiogenesis by VEGFR inhibition will complement the anti-tumor activity of an immune checkpoint inhibitor, Durvalumab, in recurrent OvCa and other solid tumors.
Objectives:
Phase I: To determine the recommended phase II dose (RP2D) and the safety of doublet therapies (Durvalumab/olaparib \[Durvalumab+O\] and Durvalumab/cediranib \[Durvalumab+C\]) and triplet therapy (Durvalumab+O+C) in patients with advanced solid tumors.
Phase II Cohort 2 non-small cell lung cancer (NSCLC); Durvalumab+O and Durvalumab+C arms: To determine clinical efficacy as measured by progression-free survival (PFS)
Phase II Cohort 3 small cell lung cancer (SCLC); Durvalumab+O arm: To determine clinical efficacy as measured by ORR
Phase II Cohort 4 metasttaic castrate-resistant prostate cancer (mCRPC); Durvalumab+O arm: To determine clinical efficacy as measured by PFS
Phase II Cohort 5 triple negative breast cancer (TNBC); Durvalumab+O arm: To determine clinical efficacy as measured by ORR
Phase II Cohort 1 OvCa; Durvalumab+O, Durvalumab+C and Durvalumab+O+C arms: To determine clinical efficacy as measured by overall response rate (ORR)
Phase II Cohort 6 colorectal cancer (CRC): C+Durvalumab arm: To determine clinical efficacy as measured by PFS
Eligibility:
Phase I: Advanced or recurrent solid tumors with evaluable disease.
Phase II Cohort 1 Durvalumab+O, Durvalumab+C and Durvalumab+O+C arms: Advanced or recurrent OvCa
Phase II Cohort 2 Durvalumab+O and Durvalumab+C arms: Advanced or recurrent NSCLC
Phase II Cohort 3 Durvalumab+O arm: Advanced or recurrent SCLC
Phase II Cohort 4 Durvalumab+O arm: mCRPC
Phase II Cohort 5 Durvalumab+O arm: Advanced or recurrent TNBC
Phase II Cohort 6 C+Durvalumab arm: Advanced or recurrent CRC
Patients must be off prior chemotherapy, radiation therapy or biologic therapy for at least 3 weeks. mCPRC patients (Cohort 4) may be on hormonal therapy with GnRH agonists/antagonists.
Adults with ECOG performance status 0-2, and adequate organ and marrow function.
Design:
Phase I: Durvalumab+O, Durvalumab+C and Durvalumab+O+C will dose escalate simultaneously. Durvalumab will be administered once every 2 weeks or once every 4 weeks until disease progression. O tablets and C will be given orally on a continuous or intermittent dosing schedule. The DLT period will be one cycle, 28 days. Patients on the 2-week schedule greater than one year will be changed to the 4-week schedule until progression.
Durvalumab+O: Durvalumab (3 mg/kg or 10 mg/kg IV every 2 weeks, or a fixed dose of 1500 mg every 4 weeks) and O tablets (150 mg or 200 mg or 300 mg BID)
Durvalumab+C: Durvalumab (3 mg/kg or 10 mg/kg IV every 2 weeks, or a fixed dose of 1500 mg every 4 weeks) and C (15 mg or 20 mg or 30 mg daily or 5 days/week)
Durvalumab+O+C: Durvalumab (a fixed dose of 1500mg every 4 weeks) with O tablets (200 mg or 300 mg BID) and C (15 mg or 20 mg 5 days/week)
Phase II Cohort 1 OvCa Durvalumab+O arm: Patients will be treated with Durvalumab+O at RP2D (O 300mg tablets bid daily and Durvalumab at 1500 mg IV every 4 weeks).
Phase II Cohort 1 OvCa Durvalumab+C arm: Patients will be treated with Durvalumab+C at RP2D (C 20mg once a day \[5 days on/2 days off\] and Durvalumab at 1500 mg every 4 weeks).
Phase II Cohort 1 OvCa Durvalumab+O+C arm: Patients with OvCa (Cohort 1) will be treated with RP2D (O tablets 300mg BID, C 20mg once a day \[5 days on/2 days off\] and Durvalumab at 1500 mg every 4 weeks).
Phase II Cohort 2 NSCLC; Durvalumab+O arm: Patients will be treated with Durvalumab+O at RP2D (O 300mg tablets bid daily and Durvalumab at 1500 mg IV every 4 weeks).
Phase II Cohort 2 NSCLC; Durvalumab+C arm: Patients will be treated with Durvalumab+C at RP2D (C 20mg once a day \[5 days on/2 days off\] and Durvalumab at 1500 mg every 4 weeks).
Phase II Cohort 3 SCLC; Durvalumab+O arm: Patients will be treated with Durvalumab+O at RP2D (O 300mg tablets bid daily and Durvalumab at 1500 mg IV every 4 weeks).
Phase II Cohort 4 mCRPC; Durvalumab+O arm: Patients will be treated with Durvalumab+O at RP2D (O 300mg tablets bid daily and Durvalumab at 1500 mg IV every 4 weeks).
Phase II Cohort 5 TNBC; Durvalumab+O arm: Patients will be treated with Durvalumab+O at RP2D (O 300mg tablets bid daily and Durvalumab at 1500 mg IV every 4 weeks).
Phase II Cohort 6 CRC; C+Durvalumab arm: Patients in the Cohort 6 will be treated with C 20mg daily alone for 14 days followed by the combination at RP2D (C 20mg once a day \[5 days on/2 days off\] and Durvalumab at 1500 mg every 4 weeks).
Phase II Correlative studies: Research samples including whole blood, CTCs, cell free DNA and plasma will be obtained at pretreatment, prior to cycle 1 day 15, prior to cycle 3 day 1 and at progression. Mandatory baseline core biopsy and two optional biopsies will be obtained.
Patients will be evaluated for toxicity every 4 weeks by CTCAEv4.0, and for response every two cycles (8 weeks) by RECIST 1.1. Patients with mCRPC (Durvalumab+O Cohort 4) will be evaluated for response initially at 8 weeks then every 12 weeks using RECIST v1.1 criteria as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2).
Disruption of the immune checkpoint PD-1/PD-L1 pathway yielded clinical activity in subsets of advanced solid tumors, such as melanoma and lung cancer.
Olaparib (O), a PARP inhibitor (PARPi), has demonstrated single agent activity in recurrent ovarian cancer (OvCa), and subsets of prostate, triple negative breast or lung cancers.
Our recent randomized phase 2 study showed that O and cediranib (C), a VEGFR1-3 inhibitor was clinically superior to O alone in platinum-sensitive recurrent OvCa.
We hypothesize that increased DNA damage by PARP inhibition and/or reduced angiogenesis by VEGFR inhibition will complement the anti-tumor activity of an immune checkpoint inhibitor, Durvalumab, in recurrent OvCa and other solid tumors.
Objectives:
Phase I: To determine the recommended phase II dose (RP2D) and the safety of doublet therapies (Durvalumab/olaparib \[Durvalumab+O\] and Durvalumab/cediranib \[Durvalumab+C\]) and triplet therapy (Durvalumab+O+C) in patients with advanced solid tumors.
Phase II Cohort 2 non-small cell lung cancer (NSCLC); Durvalumab+O and Durvalumab+C arms: To determine clinical efficacy as measured by progression-free survival (PFS)
Phase II Cohort 3 small cell lung cancer (SCLC); Durvalumab+O arm: To determine clinical efficacy as measured by ORR
Phase II Cohort 4 metasttaic castrate-resistant prostate cancer (mCRPC); Durvalumab+O arm: To determine clinical efficacy as measured by PFS
Phase II Cohort 5 triple negative breast cancer (TNBC); Durvalumab+O arm: To determine clinical efficacy as measured by ORR
Phase II Cohort 1 OvCa; Durvalumab+O, Durvalumab+C and Durvalumab+O+C arms: To determine clinical efficacy as measured by overall response rate (ORR)
Phase II Cohort 6 colorectal cancer (CRC): C+Durvalumab arm: To determine clinical efficacy as measured by PFS
Eligibility:
Phase I: Advanced or recurrent solid tumors with evaluable disease.
Phase II Cohort 1 Durvalumab+O, Durvalumab+C and Durvalumab+O+C arms: Advanced or recurrent OvCa
Phase II Cohort 2 Durvalumab+O and Durvalumab+C arms: Advanced or recurrent NSCLC
Phase II Cohort 3 Durvalumab+O arm: Advanced or recurrent SCLC
Phase II Cohort 4 Durvalumab+O arm: mCRPC
Phase II Cohort 5 Durvalumab+O arm: Advanced or recurrent TNBC
Phase II Cohort 6 C+Durvalumab arm: Advanced or recurrent CRC
Patients must be off prior chemotherapy, radiation therapy or biologic therapy for at least 3 weeks. mCPRC patients (Cohort 4) may be on hormonal therapy with GnRH agonists/antagonists.
Adults with ECOG performance status 0-2, and adequate organ and marrow function.
Design:
Phase I: Durvalumab+O, Durvalumab+C and Durvalumab+O+C will dose escalate simultaneously. Durvalumab will be administered once every 2 weeks or once every 4 weeks until disease progression. O tablets and C will be given orally on a continuous or intermittent dosing schedule. The DLT period will be one cycle, 28 days. Patients on the 2-week schedule greater than one year will be changed to the 4-week schedule until progression.
Durvalumab+O: Durvalumab (3 mg/kg or 10 mg/kg IV every 2 weeks, or a fixed dose of 1500 mg every 4 weeks) and O tablets (150 mg or 200 mg or 300 mg BID)
Durvalumab+C: Durvalumab (3 mg/kg or 10 mg/kg IV every 2 weeks, or a fixed dose of 1500 mg every 4 weeks) and C (15 mg or 20 mg or 30 mg daily or 5 days/week)
Durvalumab+O+C: Durvalumab (a fixed dose of 1500mg every 4 weeks) with O tablets (200 mg or 300 mg BID) and C (15 mg or 20 mg 5 days/week)
Phase II Cohort 1 OvCa Durvalumab+O arm: Patients will be treated with Durvalumab+O at RP2D (O 300mg tablets bid daily and Durvalumab at 1500 mg IV every 4 weeks).
Phase II Cohort 1 OvCa Durvalumab+C arm: Patients will be treated with Durvalumab+C at RP2D (C 20mg once a day \[5 days on/2 days off\] and Durvalumab at 1500 mg every 4 weeks).
Phase II Cohort 1 OvCa Durvalumab+O+C arm: Patients with OvCa (Cohort 1) will be treated with RP2D (O tablets 300mg BID, C 20mg once a day \[5 days on/2 days off\] and Durvalumab at 1500 mg every 4 weeks).
Phase II Cohort 2 NSCLC; Durvalumab+O arm: Patients will be treated with Durvalumab+O at RP2D (O 300mg tablets bid daily and Durvalumab at 1500 mg IV every 4 weeks).
Phase II Cohort 2 NSCLC; Durvalumab+C arm: Patients will be treated with Durvalumab+C at RP2D (C 20mg once a day \[5 days on/2 days off\] and Durvalumab at 1500 mg every 4 weeks).
Phase II Cohort 3 SCLC; Durvalumab+O arm: Patients will be treated with Durvalumab+O at RP2D (O 300mg tablets bid daily and Durvalumab at 1500 mg IV every 4 weeks).
Phase II Cohort 4 mCRPC; Durvalumab+O arm: Patients will be treated with Durvalumab+O at RP2D (O 300mg tablets bid daily and Durvalumab at 1500 mg IV every 4 weeks).
Phase II Cohort 5 TNBC; Durvalumab+O arm: Patients will be treated with Durvalumab+O at RP2D (O 300mg tablets bid daily and Durvalumab at 1500 mg IV every 4 weeks).
Phase II Cohort 6 CRC; C+Durvalumab arm: Patients in the Cohort 6 will be treated with C 20mg daily alone for 14 days followed by the combination at RP2D (C 20mg once a day \[5 days on/2 days off\] and Durvalumab at 1500 mg every 4 weeks).
Phase II Correlative studies: Research samples including whole blood, CTCs, cell free DNA and plasma will be obtained at pretreatment, prior to cycle 1 day 15, prior to cycle 3 day 1 and at progression. Mandatory baseline core biopsy and two optional biopsies will be obtained.
Patients will be evaluated for toxicity every 4 weeks by CTCAEv4.0, and for response every two cycles (8 weeks) by RECIST 1.1. Patients with mCRPC (Durvalumab+O Cohort 4) will be evaluated for response initially at 8 weeks then every 12 weeks using RECIST v1.1 criteria as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2).
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 15-C-0145 | None | None | View |