Copanlisib + Rucaparib for Prostate Cancer

Recruiting at 1 trial location

Overseen By BrUOG

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Brown University

Must be taking: LHRH analogues

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Leukemia, CNS disease, heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 31

Duration: Up to 3 years

13 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking any systemic therapies for prostate cancer at least 21 days before starting the study treatment. Additionally, you cannot use certain medications that affect liver enzymes, specifically CYP3A4 inhibitors and inducers, during the trial. If you are on these medications, you may need to adjust or stop them.

What data supports the effectiveness of the drug combination Copanlisib and Rucaparib for prostate cancer?

Research shows that Rucaparib, one of the drugs in the combination, has been effective in treating metastatic castration-resistant prostate cancer, especially in patients with specific genetic changes (BRCA1 or BRCA2 alterations). This suggests potential effectiveness for the combination treatment. ^{1 2 3 4 5}

Is the combination of Copanlisib and Rucaparib safe for humans?

Rucaparib has been studied for prostate cancer and has a safety profile consistent with its drug class, with serious side effects in some patients. In a study, 59% of patients experienced severe side effects, and 8% stopped treatment due to these effects. No specific safety data for the combination with Copanlisib is available. ^{2 3 6 7 8}

How is the drug combination of Copanlisib and Rucaparib unique for treating prostate cancer?

The combination of Copanlisib and Rucaparib is unique because it targets prostate cancer with specific genetic alterations in DNA damage repair genes, such as BRCA1 or BRCA2, using a dual approach: Copanlisib inhibits a pathway involved in cancer cell growth, while Rucaparib is a PARP inhibitor that exploits these genetic weaknesses to kill cancer cells. ^{2 3 9 10 11}

Research Team

Benedito Carneiro, MD, MS

Principal Investigator

Brown University

Eligibility Criteria

Adults with metastatic castration-resistant prostate cancer who've progressed after certain treatments can join. They need a life expectancy of at least 3 months, acceptable organ function, and no recent serious cardiovascular events or other cancers in the last 5 years. Men must use contraception during and post-treatment for 6 months.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

My cancer has worsened despite treatment with abiraterone, enzalutamide, or apalutamide.

My organs and bone marrow are functioning well.

Exclusion Criteria

I am on immunosuppressive therapy but take 10mg/day or less of prednisone.

I have had cancer within the last 5 years.

I haven't had radiotherapy or chemo/immunotherapy in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive copanlisib and rucaparib until disease progression or unacceptable toxicity

Up to 3 years

Every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Every 3 months

Treatment Details

Interventions

• Copanlisib
• Rucaparib

Trial Overview The trial is testing a combination of two drugs: Copanlisib and Rucaparib. It's an open-label study where all participants receive the same treatment to assess safety, how the body processes the drugs, and their effectiveness against prostate cancer.

Participant Groups

Group I: Dose Level 4 Experimental Treatment 2 Interventions

600 mg Rucaparib, 60 mg Copanlisib

Group II: Dose Level 3 Experimental Treatment 2 Interventions

600 mg Rucaparib, 45 mg Copanlisib

Group III: Dose Level 2 Experimental Treatment 2 Interventions

500 mg Rucaparib, 45 mg Copanlisib

Group IV: Dose Level 1 Experimental Treatment 2 Interventions

400 mg Rucaparib, 45 mg Copanlisib

Group V: Dose Level -2 Experimental Treatment 2 Interventions

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

Group VI: Dose Level -1 Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

Rhode Island Hospital

Collaborator

Trials

275

Recruited

71,400+

The Miriam Hospital

Collaborator

Trials

252

Recruited

39,200+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Clovis Oncology, Inc.

Industry Sponsor

Trials

65

Recruited

11,100+

Patrick J. Mahaffy

Clovis Oncology, Inc.

Chief Executive Officer since 2009

BA from Haverford College, MBA from Columbia University

Lindsey Rolfe

Clovis Oncology, Inc.

Chief Medical Officer since 2015

Specialist accreditation in pharmaceutical medicine

Findings from Research

In the SPARTAN study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved health-related quality of life (HRQoL) compared to placebo, with patients maintaining better scores over time.

Patients receiving apalutamide experienced minimal side effects and reported no worsening of fatigue, while those on placebo showed a decline in quality of life after about one year, highlighting the efficacy and tolerability of apalutamide in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Oudard, S., Hadaschik, B., Saad, F., et al.[2022]

Rucaparib, a PARP inhibitor, has been granted accelerated approval for treating men with metastatic castration-resistant prostate cancer (mCRPC) who have BRCA1 or BRCA2 mutations, based on safety data from clinical trials involving 193 participants.

Common treatment-emergent adverse events (TEAEs) include gastrointestinal issues, fatigue, and anemia, with most being self-limiting; effective management of these TEAEs is crucial to maximize the benefits of rucaparib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for Management of Treatment-Emergent Adverse Events During Rucaparib Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. Labadie, BW., Morris, DS., Bryce, AH., et al.[2022]

In the IPATential150 trial involving 1097 patients with metastatic castration-resistant prostate cancer, adding ipatasertib to abiraterone and prednisone significantly improved radiographic progression-free survival for patients with PTEN-loss tumors.

While ipatasertib was associated with a higher rate of serious adverse events and treatment discontinuation compared to placebo, its overall safety profile was considered tolerable, suggesting that with proper management, the side effects could be mitigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. Matsubara, N., de Bono, J., Sweeney, C., et al.[2023]

In a phase Ib trial involving 51 patients with metastatic castration-resistant prostate cancer (mCRPC), the combination of ipatasertib and rucaparib was found to be manageable, with a recommended phase II dose established, but resulted in a modest prostate-specific antigen (PSA) response rate of only 26%.

While the treatment was associated with significant adverse events (46% of patients experienced grade 3/4 events), there were no deaths, and the median overall survival was reported at 13.3 months, indicating that while the combination was tolerable, it did not show strong antitumor activity in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib, Open-label Study Evaluating the Safety and Efficacy of Ipatasertib plus Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer. Pook, D., Geynisman, DM., Carles, J., et al.[2023]

In the TRITON2 study involving 78 patients with metastatic castration-resistant prostate cancer (mCRPC) and non-BRCA DNA damage repair (DDR) gene alterations, limited responses to the PARP inhibitor rucaparib were observed, particularly in patients with ATM, CDK12, or CHEK2 alterations.

However, some patients with alterations in other DDR genes like PALB2, FANCA, BRIP1, and RAD51B showed potential benefits from PARP inhibition, suggesting that not all DDR alterations respond similarly to this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study. Abida, W., Campbell, D., Patnaik, A., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration: Final Results from the Phase 2 TRITON2 Study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Rucaparib or Physician's Choice in Metastatic Prostate Cancer. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Phase II evaluation of early oral estramustine, oral etoposide, and intravenous paclitaxel combined with hormonal therapy in patients with high-risk metastatic prostate adenocarcinoma: Southwest Oncology Group S0032. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Guidelines for Management of Treatment-Emergent Adverse Events During Rucaparib Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA-Mutated Metastatic Castrate-Resistant Prostate Cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

The growing role of rucaparib in contemporary treatment of metastatic prostate cancer: a review of efficacy and guidance for side effect management. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

A Phase Ib, Open-label Study Evaluating the Safety and Efficacy of Ipatasertib plus Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study. [2021]