Testing the Safety of the Anti-Cancer Drugs Durvalumab and Olaparib During Radiation Therapy for Locally Advanced Unresectable Pancreatic Cancer
A Phase 1 Study of Olaparib in Combination With Durvalumab (MEDI4736) and Concurrent Radiation Therapy Following First-Line Chemotherapy in Locally Advanced Unresectable Pancreatic Cancer
4 other identifiers
interventional
18
2 countries
11
Brief Summary
This phase I trial tests the safety and tolerability of olaparib in combination with durvalumab and radiation therapy in patients with pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable). Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. The combination of targeted therapy with olaparib, immunotherapy with durvalumab and radiation therapy may stimulate an anti-tumor immune response and promote tumor control in locally advanced unresectable pancreatic cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2023
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 8, 2022
CompletedFirst Posted
Study publicly available on registry
June 9, 2022
CompletedStudy Start
First participant enrolled
May 22, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2028
April 30, 2026
December 1, 2025
3.1 years
June 8, 2022
April 29, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Dose-limiting toxicities (DLTs) for olaparib in combination with durvalumab and radiation
The numbers of subjects treated at each dose level and DLT incidence in both components will be summarized. Will report the estimate probability of DLT with 95% Bayesian Credible Intervals for each dose level as estimated by the TiTE-CRM algorithm at the completion of the phase IB Part 2.
From start of radiation therapy for up to 6 weeks
Secondary Outcomes (6)
Progression-free survival
From date of treatment to date of radiological or clinical progression, or death from any cause, whichever comes first, assessed up to 4 years
Relapse free survival
Up to 4 years
Overall survival
Up to 4 years
Overall response rate (ORR)
Up to 4 years
Incidence of adverse events
Up to 90 days after last dose
- +1 more secondary outcomes
Other Outcomes (1)
Correlation of efficacy endpoints with clinicopathologic variables
Up to 4 years
Study Arms (1)
Treatment (olaparib, durvalumab, radiation therapy)
EXPERIMENTALPatients receive olaparib PO BID on days 1-28 and durvalumab IV over 55-65 minutes on day 1 of each cycle. Beginning cycle 2, patients also undergo radiation therapy daily on weekdays for 3 weeks. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo Patients undergo CT scan with or without MRI and collection of blood samples throughout the study. Patients may undergo optional collection of buccal samples and optional biopsy at screening and/or on study.
Interventions
Undergo CT scan
Given IV
Undergo MRI
Given PO
Undergo biopsy
Undergo collection of blood and buccal samples
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed pancreatic cancer (excluding islets) (not otherwise specified \[NOS\]) (Medical Dictionary for Regulatory Activities \[MEDDRA\] code: 10033612).
- Patients must have unresectable locally advanced pancreatic cancer as determined by a multidisciplinary tumor board applying National Comprehensive Cancer Network (NCCN) version (v)2.2021 criteria or as surgically determined during failed resection attempt.
- Patients must have had prior first-line chemotherapy for this cancer for at least 16 weeks without clinical, biochemical, or radiologic progression. There should be a washout of at least 2 weeks from first-line chemotherapy and start of therapy on clinical trial.
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of durvalumab and olaparib in combination with radiation in patients \< 18 years of age, children are excluded from this study.
- Body weight \> 30 kg.
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%).
- Hemoglobin \>= 9.0 g/dL without blood transfusion in last 4 weeks (within 2 weeks of enrollment).
- Absolute neutrophil count \>= 1,500/mcL (within 2 weeks of enrollment).
- Platelets \>= 100,000/mcL (within 2 weeks of enrollment).
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 2 weeks of enrollment).
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine transferase (ALT) (serum glutamic pyruvic transaminase) \[SGPT\]) =\< 2.5 x institutional ULN (within 2 weeks of enrollment).
- Creatinine =\< 1.5 x institutional ULN (within 2 weeks of enrollment).
- Measured creatinine clearance \> 60 mL/min/1.73 m\^2 (within 2 weeks of enrollment).
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- +18 more criteria
You may not qualify if:
- Patients who have had prior upper abdominal radiotherapy prior to entering the study.
- Patients with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
- Major surgical procedure within 28 days prior to enrollment. Note: Local surgery of isolated lesions for palliative intent is acceptable. Laparoscopy and/or laparotomy without resection does not constitute a major surgical procedure.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
- Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Receipt of live attenuated vaccine within 30 of planned start of study therapy. Note: Patients, if enrolled, should not receive live vaccine whilst receiving investigational product (IP) and up to 30 days after the last dose of IP.
- Patients who are receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib or durvalumab.
- Patients with any other significant condition(s) that would make this protocol unreasonably hazardous.
- Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4/5 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital, and 3 weeks for other agents.
- Must not have prior history of organ transplantation, allogeneic transplantation, or double umbilical cord transplantation.
- Must not have germline BRCA1 or BRCA2 mutation.
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
University of Michigan - Brighton Center for Specialty Care
Brighton, Michigan, 48116, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Vaibhav Sahai
University of Michigan Comprehensive Cancer Center EDDOP
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 8, 2022
First Posted
June 9, 2022
Study Start
May 22, 2023
Primary Completion (Estimated)
July 1, 2026
Study Completion (Estimated)
July 1, 2028
Last Updated
April 30, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.