Copanlisib + Rucaparib for Prostate Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for prostate cancer that has spread and resists standard hormonal therapy. It involves two drugs: copanlisib, a kinase inhibitor, and rucaparib, a PARP inhibitor, to determine if they can control the disease. The trial tests different doses to find the safest and most effective approach. Men with prostate cancer that progresses despite treatments like abiraterone or enzalutamide might be suitable candidates. Participants will continue treatment as long as they benefit without significant side effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of copanlisib and rucaparib has been studied before. In one study, 59% of patients experienced severe side effects, and 8% discontinued treatment due to these effects. This suggests that while the treatment may be effective, it can also cause serious side effects for some individuals.

For rucaparib alone, nearly all patients (99.7%) experienced side effects, with 46.4% facing serious ones. This indicates that while rucaparib can be effective, it may also lead to serious issues for many users.

Overall, the combination of copanlisib and rucaparib presents both potential benefits and risks. These factors are important to consider when deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Copanlisib and Rucaparib for prostate cancer because these drugs target cancer cells in unique ways compared to standard treatments like hormone therapy and chemotherapy. Copanlisib inhibits specific enzymes (PI3K) that help cancer cells grow, while Rucaparib blocks PARP enzymes, preventing cancer cells from repairing themselves. This dual approach could potentially enhance the effectiveness of treatment by attacking the cancer on two fronts, offering hope for better outcomes in prostate cancer management.

What evidence suggests that the combination of copanlisib and rucaparib might be an effective treatment for metastatic castration-resistant prostate cancer?

Research has shown that combining the drugs copanlisib and rucaparib may help treat advanced prostate cancer that no longer responds to hormone therapy. This trial will administer varying doses of this combination to participants to assess its effectiveness and safety. One study found that about 28% of patients experienced a significant drop in their PSA levels, a test used to monitor prostate cancer. This suggests the treatment might slow cancer growth in some patients. However, 59% of patients experienced serious side effects, and 8% stopped treatment due to these effects. While these early results are promising, more research is needed to fully understand the safety and effectiveness of this treatment. ^{1 2 3 4 5}

Who Is on the Research Team?

Benedito Carneiro, MD, MS

Principal Investigator

Brown University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.128

BrUOG360: A phase Ib/II study of copanlisib combined with ... The RP2D was rucaparib 400mg BID with copanlisib 45mg (D1, D15; 28-day cycle). There were 2 confirmed PSA50 responses among 7 evaluable pts (28%). One pt had ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04253262

NCT04253262 | A Study of Copanlisib Combined With ... To estimate the overall response rate of the combination of copanlisib and rucaparib in patients with metastatic castration-resistant prostate cancer.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9675324/

Role of Rucaparib in the Treatment of Prostate Cancer For example, data from the US has shown that both localized and regional tumors have a 5-year relative survival rate of >99%. Once the tumor has ...

4. withpower.com withpower.com/trial/phase-2-prostatic-neoplasms-3-2020-868a3

Copanlisib + Rucaparib for Prostate Cancer 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 ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT449686

PLATIPARP: A phase 2 study of induction docetaxel and ... 20 patients provided ~90% power to determine whether this treatment lowered risk of progression with a hazard ratio of 0.5 (implying PFS of 18.2 months), based ...