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 range

18 Years

Sex

ALL

See this in plain English?

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…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

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