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
National Cancer Institute (NCI)
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.
Description
PRIMARY OBJECTIVE: I. Determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of olaparib in combination with durvalumab and radiation therapy (RT). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. Correlate response with the circulating frequency and diversity of T cells within the peripheral blood. III. Evaluate the safety and toxicity of olaparib in combination with durvalumab and RT. EXPLORATORY OBJECTIVES: I. Evaluate the genetic and clinicopathologic markers of response and resistance including prior receipt of platinum therapy. II. To cor…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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 r…
Interventions
- ProcedureBiopsy Procedure
Undergo biopsy
- ProcedureBiospecimen Collection
Undergo collection of blood and buccal samples
- ProcedureComputed Tomography
Undergo CT scan
- BiologicalDurvalumab
Given IV
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- DrugOlaparib
Given PO
Locations (11)
- UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareIrvine, California
- Los Angeles General Medical CenterLos Angeles, California
- USC / Norris Comprehensive Cancer CenterLos Angeles, California
- UC Irvine Health/Chao Family Comprehensive Cancer CenterOrange, California
- University of Michigan Rogel Cancer CenterAnn Arbor, Michigan
- University of Michigan - Brighton Center for Specialty CareBrighton, Michigan