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Active Not RecruitingNCT03842228

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

A Phase 1b Biomarker-Driven Combination Trial of Copanlisib, Olaparib, and Durvalumab (MEDI4736) in Patients With Advanced Solid Tumors

Status
Active Not Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
39 (actual)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety and establish the recommended phase 2 dose (RP2D) of the doublet combination of copanlisib and olaparib and of the triplet combination of copanlisib, olaparib and MEDI4736 (durvalumab) in patients with molecularly-selected solid tumors. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity of the doublet combination of copanlisib and olaparib, and of the triplet combination of copanlisib, olaparib and MEDI4736 (durvalumab) in patients with molecularly-selected advanced solid tumors, as measured by objective response rate (ORR) (complete response \[CR\] + partial response \[PR\]). Although the clinical benefit of the doublet and triplet combination of these drugs has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. II. To assess overall duration of response (DoR), progression free survival (PFS) and overall survival (OS). III. To assess the pharmacokinetic (PK) profiles of these combinations, and explore exposure-response relationships. IV. To correlate molecular alterations with OR (CR+PR). OUTLINE: This is a dose-escalation and expansion study of the doublet combination of copanlisib and olaparib or the triplet combination of copanlisib, olaparib, durvalumab. In the dose escalation phase of the study, patients treated with the doublet combination will receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1 and 15 or days 1, 8, and 15 depending on dose level and olaparib orally (PO) twice daily (BID) on days 1-28 of each cycle. Patients treated with the triplet combination will also receive copanlisib hydrochloride and olaparib, in addition to also receiving durvalumab beginning in cycle 2. Beginning in cycle 2, patients treated with the triplet combination will receive durvalumab IV over 1 hour on day 1 of each cycle. In the dose expansion phase of the study, patients will be treated with the best study drug dose identified in the dose escalation phase of the study. For all patients treated with the doublet and triplet combinations, the cycles will repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples at baseline within 7 days of cycle 1 day 1 (C1D1), days 8 and 15 of cycle 1 and day 15 of subsequent cycles, at time of restaging, and end of treatment/progression. Patients undergo x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) at the end of cycle 2 and then every 8 weeks. Patients also undergo an echocardiography (ECHO) during pre-study within 28 days of C1D1 and tumor biopsy at baseline within 7 days of C1D1 and day 15 of cycle 1 or 2, and may undergo an optional biopsy at end of treatment/progression. After completion of study treatment, all patients are followed up at 30 days and then every 3 months for up to 2 years.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiopsy ProcedureUndergo tumor biopsy
PROCEDUREBiospecimen CollectionUndergo collection of blood samples
PROCEDUREComputed TomographyUndergo CT
DRUGCopanlisib HydrochlorideGiven IV
BIOLOGICALDurvalumabGiven IV
PROCEDUREEchocardiography TestUndergo ECHO
PROCEDUREMagnetic Resonance ImagingUndergo MRI
DRUGOlaparibGiven PO
PROCEDUREX-Ray ImagingUndergo x-ray

Timeline

Start date
2019-11-21
Primary completion
2024-07-29
Completion
2026-09-24
First posted
2019-02-15
Last updated
2025-10-14
Results posted
2025-08-03

Locations

17 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03842228. Inclusion in this directory is not an endorsement.