A Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer

NCT04253262 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BrUOG 360
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single arm Phase Ib/II, open label, safety, pharmacokinetic and efficacy clinical study in adult patients with metastatic castration-resistant prostate cancer (mCRPC). Patients will be treated with the combination of copanlisib and rucaparib for as long as the patient does not have clinically significant progressive disease and/or unacceptable toxicity and/or as long as the investigator deems that the patient is benefiting from treatment. Treatment may also be stopped if the patient withdraws consent, or study termination occurs.

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose

  To evaluate the maximum tolerated dose of copanlisib with rucaparib in patients with metastatic castration-resistant prostate cancer.

  Cycle 1 (each cycle is 28 days) through pre-dosing cycle 2, approximately 1 month.

• Response

  To estimate the overall response rate of the combination of copanlisib and rucaparib in patients with metastatic castration-resistant prostate cancer.

  Every 28 days on treatment, then every 3 months until progression of disease up to 3 years.

Study Arms (6)

Dose Level -2

EXPERIMENTAL

300 mg Rucaparib, 45 mg (day 1 \& 15) Copanlisib

Drug: Rucaparib; Drug: Copanlisib

Dose Level -1

EXPERIMENTAL

400 mg Rucaparib, 45 mg (day 1 \& 15) Copanlisib

Drug: Rucaparib; Drug: Copanlisib

Dose Level 1

EXPERIMENTAL

400 mg Rucaparib, 45 mg Copanlisib

Drug: Rucaparib; Drug: Copanlisib

Dose Level 2

EXPERIMENTAL

500 mg Rucaparib, 45 mg Copanlisib

Drug: Rucaparib; Drug: Copanlisib

Dose Level 3

EXPERIMENTAL

600 mg Rucaparib, 45 mg Copanlisib

Drug: Rucaparib; Drug: Copanlisib

Dose Level 4

EXPERIMENTAL

600 mg Rucaparib, 60 mg Copanlisib

Drug: Rucaparib; Drug: Copanlisib

Interventions

Rucaparib DRUG

Rucaparib (PO twice daily continuous)

Also known as: Rubraca

Dose Level -1; Dose Level -2; Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

Copanlisib DRUG

Copanlisib (IV day 1, 8, 15; 28 day cycle)

Also known as: Aliqopa

Dose Level -1; Dose Level -2; Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Life expectancy of at least 3 months
• Histologically confirmed prostate cancer. Treatment-emergent small cell/NEPC (neuroendocrine prostate cancer) is allowed, but de novo small cell carcinoma of the prostate is excluded.
• Progressive metastatic prostate cancer despite castrate levels of testosterone (\< 50 ng/dL).
• Patients may have either non-measurable disease OR measurable disease (by RECIST criteria)
• Progressive disease during treatment (or within 4 weeks of completion) with abiraterone, enzalutamide, and/or apalutamide based on any one of the following:
• For patients with measurable disease, progression by the RECIST 1.1 criteria
• PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least one week apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression for the purposes of eligibility
• Radionuclide bone scan: At least two new foci consistent with metastatic lesions
• Testosterone \< 50 ng/dL. Patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone bilateral orchiectomy.
• Prior therapy with taxane in the castrate-sensitive or castration-resistant settings will be allowed. Prior treatment with radium-223 or sipuleucel-T is permitted, but not required.
• No other systemic therapies for prostate cancer within 21 days prior to cycle 1 day 1 of study therapy or 5 half-lives, whichever is shorter, prior to day 1 of study therapy.
• Left ventricular ejection fraction (LVEF) ≥ 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) obtained during screening
• Absolute Neutrophil Count ≥ 1,500/mm3

You may not qualify if:

• History of myelodysplastic syndrome or acute myeloid leukemia.
• During phase 2, patients must not have received previous treatment with a DNA-damaging cytotoxic chemotherapy (e.g. prior platinum-based chemotherapy and mitoxantrone are not permitted) or PARP inhibitor. Prior treatment with PARP inhibitor is allowed during phase I dose escalation.
• Untreated leptomeningeal or metastatic CNS disease; patients with treated disease may be eligible if clinically stable for 4 weeks after radiation or surgery including those with history of spinal cord compression that have received definitive treatment. If patients are receiving steroids as adjunct for treatment of leptomeningeal disease or metastatic CNS disease, dose should be stable for 4 weeks prior to day 1 of cycle 1.
• Clinically significant, uncontrolled heart disease and/or recent events including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within 6 months prior to screening
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening. Patients with rate-controlled atrial fibrillation or flutter are permitted.
• QTcF \> 470 msec on screening 12-lead ECG
• Documented cardiomyopathy
• Clinically significant uncontrolled hypertension (systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management). For the purpose of this protocol definition of uncontrolled hypertension is based on persistent (≥72 hours) and symptomatic.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication. However, patients with a venous thrombosis, including a pulmonary embolus, who have been on stable anticoagulation (more than 1 month without bleeding on a stable dose) is permitted. Patients with evidence or history of uncontrolled bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication
• History or concurrent condition of clinically significant interstitial lung disease and/or severely impaired lung function. History of renal failure requiring peritoneal dialysis or hemodialysis. History of cirrhosis Child-Pugh B or C. Intestinal malabsorption.
• Active, clinically serious infections of CTCAE (v 5.0) Grade ≥ 2 or per investigator discretion.
• History of uncontrolled human immunodeficiency virus (HIV) infection defined as CD4 \< 200 cells/mm3 or detectable viral load is not allowed.
• Hepatitis B (HBV) or hepatitis C (HCV). All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel. Patients positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA. These patients should receive prophylactic antiviral therapy. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.

Sponsors & Collaborators

• Brown University: lead
• Rhode Island Hospital: collaborator
• The Miriam Hospital: collaborator
• Bayer: collaborator
• Clovis Oncology, Inc.: collaborator

Study Sites (2)

Helen Diller Family Comprehensive Cancer Center University of California San Francisco

San Francisco, California, 94115, United States

Location

Lifespan Cancer Institute

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Interventions

rucaparib; copanlisib

Study Officials

• Benedito Carneiro, MD, MS

  Brown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose escalation will follow the standard 3+3 design. Once the maximum tolerated dose is achieved in Phase I, Phase II will proceed.

Study Record Dates

• First Submitted: January 31, 2020
• First Posted: February 5, 2020
• Study Start: April 3, 2020
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: May 4, 2025

Record last verified: 2025-05

Locations

US (2)