Metastatic Castration-resistant Prostate CancerPhase 1/2NCT04253262
A Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer
A Phase 1/2 study testing Rucaparib and Copanlisib in people with Metastatic Castration-resistant Prostate Cancer, run by Brown University at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castration-resistant Prostate Cancer
- What is being tested?
- Rucaparib and Copanlisib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Apr 2020to Jan 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- Patients must have adequate organ and bone marrow function within 14 days of inclusion in the study as defined below:
- Absolute Neutrophil Count ≥ 1,500/mm3
- Hemoglobin ≥ 9 g/dL
- Platelets ≥ 100,000 /mm3
- PT/INR ≤ 1.5 x ULN unless on chronic and stable anticoagulation at time of study entry
- Bilirubin ≤1.5 x institutional upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's Syndrome, who can have total bilirubin <3.0 mg/dL
- AST/ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases present)
- Lipase ≤ 1.5 x ULN
- HbA1c < 8.5 %
- Serum Creatinine ≤ 1.5 X ULN (upper limit of normal) or creatinine clearance ≥ 45 mL/minute (using Cockcroft/Gault formula)
- Sexually active males must use a condom with spermicide during intercourse while taking the drug and for 6 months after stopping treatment, even if patient is vasectomized to prevent delivery of the drug via seminal fluid.
- Patients must agree to provide tumor tissue, either fresh or archival specimen of primary tumor and/or metastatic lesion, if available. Availability of tissue will not be required for enrollment.
- Subjects must have the ability to understand and the willingness to sign a written informed consent prior to registration on study. Subjects should be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations at the institution.
- Only during phase 2, patients will be required to have mutations in DNA repair genes based on molecular tests performed on germline DNA, prostate cancer tissue or ctDNA. Qualifying mutations (i.e. deleterious/pathogenic alterations) in at least one of the following genes involved with homologous recombination repair will be required: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, FANCL, FANCA, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L. Variants of unknown significance in one of the above genes are not eligible.
Who cannot join
- 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)
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- 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.
- Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated cervical carcinoma in situ, non-melanoma skin cancer, superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) or other T1 tumor that has been surgically removed with a low chance of recurrence in the next 3 years.
- Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation
- Ongoing substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
- Prior radiation within 7 days of start drug. Prior major surgery, open biopsy or significant trauma within 28 days of start drug.
- Patients with severe psychiatric illness/social situations that would limit compliance with study requirements in the judgment of study investigator
- Patient has a history of non-compliance to medical regimen or inability to grant consent
- Ongoing immunosuppressive therapy. Patients may be receiving up to 10mg/day of prednisone.
- Radiotherapy or immuno-/chemotherapy less than 2 weeks before start of treatment. A wash-out period of 2 months from radiopharmaceuticals such as radium-223 and 177Lu-PSMA among others will be required.
- Myeloid growth factors within 14 days prior to treatment.
- Blood or platelet transfusion less than 7 days before cycle 1 day 1.
- History of having received an allogeneic bone marrow or organ transplant.
- Major surgical procedure or significant traumatic injury (as judged by the investigator) within 28 days before start of treatment, or have not recovered from major side effects; open biopsy within 7 days before start of treatment.
- Anti-arrhythmic therapy for ventricular arrhythmias. Use of amiodarone and propafenone for atrial fibrillation rate control is allowed.
- Use of CYP3A4 inhibitors and inducers. Copanlisib is primarily metabolized by CYP3A4. Therefore concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, darunavir, indinavir, lopinavir, mifepristone, posaconazole, ombitasvir, idelalisib, cobicistat, atazanavir, ritonavir, indinavir, nelfinavir and saquinavir) and inducers (apalutamide, carbamazepine, enzalutamide, fosphenytoin, phenobarbital, phenytoin, primidone, rifampin) is not allowed. Rucaparib is a moderate inhibitor of CYP1A2 and a weak inhibitor of CYP2C9, CYP2C19 and CYP3A4 and no specific medications is contra-indicated but dose adjustment may be necessary of concurrent medication
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Lifespan Cancer Institute
Providence, Rhode Island, 02903
Helen Diller Family Comprehensive Cancer Center University of California San Francisco
San Francisco, California, 94115
About this study
Official title: A Phase Ib/II Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer
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.
- Being tested
- Rucaparib, Copanlisib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RucaparibDrug
Also called Rubraca
Rucaparib (PO twice daily continuous)
CopanlisibDrug
Also called Aliqopa
Copanlisib (IV day 1, 8, 15; 28 day cycle)
| Study group | Role | What they receive |
|---|---|---|
| Dose Level -2 | Experimental | 300 mg Rucaparib, 45 mg (day 1 \& 15) Copanlisib Receives: Drug: Rucaparib; Drug: Copanlisib |
| Dose Level -1 | Experimental | 400 mg Rucaparib, 45 mg (day 1 \& 15) Copanlisib Receives: Drug: Rucaparib; Drug: Copanlisib |
| Dose Level 1 | Experimental | 400 mg Rucaparib, 45 mg Copanlisib Receives: Drug: Rucaparib; Drug: Copanlisib |
| Dose Level 2 | Experimental | 500 mg Rucaparib, 45 mg Copanlisib Receives: Drug: Rucaparib; Drug: Copanlisib |
| Dose Level 3 | Experimental | 600 mg Rucaparib, 45 mg Copanlisib Receives: Drug: Rucaparib; Drug: Copanlisib |
| Dose Level 4 | Experimental | 600 mg Rucaparib, 60 mg Copanlisib Receives: Drug: Rucaparib; Drug: Copanlisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
To evaluate the maximum tolerated dose of copanlisib with rucaparib in patients with metastatic castration-resistant prostate cancer.
Measured: 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.
Measured: Every 28 days on treatment, then every 3 months until progression of disease up to 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start3 Apr 2020
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by Brown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose escalation will follow the standard 3+3 design. Once the maximum tolerated dose is achieved in Phase I, Phase II will proceed.
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- Rhode Island Hospital, The Miriam Hospital, Bayer, Clovis Oncology, Inc.
- Responsible party
- Sponsor
- Investigators
- Benedito Carneiro, MD, MS, Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04253262
- Sponsor's protocol ID
- BrUOG 360
- Status last verified
- May 2025
- First submitted
- 31 Jan 2020
- Last updated
- 4 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT04253262
- Acronym / sponsor ID
- BrUOG 360
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- Rhode Island Hospital, The Miriam Hospital, Bayer, Clovis Oncology, Inc.
- Study start
- 3 Apr 2020 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 5 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Dose escalation will follow the standard 3+3 design. Once the maximum tolerated dose is achieved in Phase I, Phase II will proceed.
| Arm | Type | Receives |
|---|---|---|
| Dose Level -2 | Experimental | Drug: Rucaparib, Drug: Copanlisib300 mg Rucaparib, 45 mg (day 1 \& 15) Copanlisib |
| Dose Level -1 | Experimental | Drug: Rucaparib, Drug: Copanlisib400 mg Rucaparib, 45 mg (day 1 \& 15) Copanlisib |
| Dose Level 1 | Experimental | Drug: Rucaparib, Drug: Copanlisib400 mg Rucaparib, 45 mg Copanlisib |
| Dose Level 2 | Experimental | Drug: Rucaparib, Drug: Copanlisib500 mg Rucaparib, 45 mg Copanlisib |
| Dose Level 3 | Experimental | Drug: Rucaparib, Drug: Copanlisib600 mg Rucaparib, 45 mg Copanlisib |
| Dose Level 4 | Experimental | Drug: Rucaparib, Drug: Copanlisib600 mg Rucaparib, 60 mg Copanlisib |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- 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).
Key exclusion criteria (29 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RucaparibAlso: RubracaRucaparib (PO twice daily continuous) | Drug | Dose Level -1, Dose Level -2, Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4 |
| CopanlisibAlso: AliqopaCopanlisib (IV day 1, 8, 15; 28 day cycle) | Drug | Dose Level -1, Dose Level -2, Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4 |
Primary outcome
Maximum Tolerated Dose
Time frame: Cycle 1 (each cycle is 28 days) through pre-dosing cycle 2, approximately 1 month.
To evaluate the maximum tolerated dose of copanlisib with rucaparib in patients with metastatic castration-resistant prostate cancer.
Response
Time frame: Every 28 days on treatment, then every 3 months until progression of disease up to 3 years.
To estimate the overall response rate of the combination of copanlisib and rucaparib in patients with metastatic castration-resistant prostate cancer.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2025.
Related trials for Metastatic Castration-resistant Prostate Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Castration-resistant Prostate Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benedito Carneiro, MD, MS principal investigator
Brown University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Rucaparib and Copanlisib in people with Metastatic Castration-resistant Prostate Cancer, run by Brown University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: Cycle 1 (each cycle is 28 days) through pre-dosing cycle 2, approximately 1 month.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2025.