Active — Not RecruitingPhase 1

Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations

United States39 participantsStarted 2019-11-21

Plain-language summary

This phase Ib trial seeks to identify the side effects and best dose of the combination of copanlisib and olaparib when given together with durvalumab. The trial will evaluate how well the drug combinations work in treating patients with advanced cancers who have solid tumors that have spread from where they first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves and may stop growing. 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. The treatment combinations of copanlisib and olaparib or copanlisib, olaparib, and durvalumab may work better in treating patients with solid tumors compared to usual treatments such as surgery, radiation, or other chemotherapy drugs.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * ELIGIBILITY CRITERIA FOR ENROLLMENT INTO STEPS 1, 2, AND 3 * Patients must have germline or somatic mutations in DDR genes: BARD1, BRCA1, BRCA2, BRIP1, FANCA, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D; or actionable mutations in the PTEN gene, or hotspot mutations in the PIK3CA gene (E542, E545 or H1047 are accepted). Local testing in Clinical Laboratory Improvement Act (CLIA)-certified laboratory will be accepted. Only mutations that have been recognized as actionable by the MD Anderson Precision Oncology Decision Support (PODS) team will be accepted * Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective * Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Patients must be \>= 3 weeks beyond treatment with any chemotherapy or \>= 4 weeks beyond treatment with other investigational therapy to include hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation * Age \>= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of copanlisib in combination with olaparib +/- durvalumab (MEDI4736) in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials * Patients with a mutat…

What they're measuring

Number of Patients With Dose Limiting Toxicities (DLT) as a Measure of Safety Profile to Determine Recommended Phase 2 Dose (RP2D)

Timeframe: The DLT monitoring time frame was Cycle 1 through Cycle 2 Day 1 for the doublet combination (SIL1, SIL2, SIL3, and SIL3A) , and Cycle 1 through Cycle 3 Day 1 for the triplet combination (S2L1)

Trial details

NCT IDNCT03842228

SponsorNational Cancer Institute (NCI)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2024-07-29

Results submitted2025-07-21

View on ClinicalTrials.gov More Advanced Malignant Solid Neoplasm trials