61 Participants Needed

Rucaparib + Enzalutamide for Prostate Cancer

(CASPAR Trial)

Recruiting at 438 trial locations
AR
Overseen ByArpit Rao, MD
Age: 18+
Sex: Male
Trial Phase: Phase 3
Sponsor: Alliance for Clinical Trials in Oncology
Must be taking: Androgen deprivation
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This randomized, placebo-controlled phase III trial is evaluating the benefit of rucaparib and enzalutamide combination therapy versus enzalutamide alone for the treatment of men with prostate cancer that has spread to other places in the body (metastatic) and has become resistant to testosterone-deprivation therapy (castration-resistant). Enzalutamide helps fight prostate cancer by blocking the use of testosterone by the tumor cells for growth. Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors, such as rucaparib, fight prostate cancer by prevent tumor cells from repairing their DNA. Giving enzalutamide and rucaparib may make patients live longer or prevent their cancer from growing or spreading for a longer time, or both. It may also help doctors learn if a mutation in any of the homologous recombination DNA repair genes is helpful to decide which treatment is best for the patient.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are strong inhibitors of CYP2C8 or inducers of CYP3A4 enzymes before joining. You should also closely monitor any medications that are substrates of CYP3A4, CYP2C9, and CYP2C19 enzymes with your doctor.

What data supports the effectiveness of the drug combination Rucaparib + Enzalutamide for prostate cancer?

Research shows that Enzalutamide, one of the drugs in the combination, significantly improves survival and delays disease progression in men with metastatic castration-resistant prostate cancer, suggesting its potential effectiveness in similar settings.12345

Is the combination of Rucaparib and Enzalutamide safe for humans?

Enzalutamide, used for prostate cancer, has been shown to be generally safe in humans, but it can cause side effects like fatigue and, in rare cases, severe issues like low platelet counts (thrombocytopenia) and seizures. There is no specific safety data available for the combination of Rucaparib and Enzalutamide.16789

How is the drug combination of Rucaparib and Enzalutamide unique for prostate cancer treatment?

The combination of Rucaparib and Enzalutamide is unique because Rucaparib targets DNA damage repair gene alterations, such as BRCA1 or BRCA2, which are common in metastatic castration-resistant prostate cancer, while Enzalutamide is an antiandrogen that helps block the effects of male hormones that can promote cancer growth. This dual approach targets both genetic vulnerabilities and hormone-driven cancer growth.1341011

Research Team

AR

Arpit Rao, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

Men with metastatic prostate cancer resistant to testosterone-deprivation therapy are eligible. They must have documented prostate adenocarcinoma, radiographic progression, and no central nervous system metastases that aren't stable or treated. Participants need to be off certain drugs affecting liver enzymes and recovered from major surgeries or treatments. No prior treatment for metastatic castration-resistant prostate cancer is allowed.

Inclusion Criteria

I have available tissue samples from my cancer for testing.
My cancer has spread and can be measured or not.
Total bilirubin =< 1.5 x upper limit of normal (ULN)
See 33 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enzalutamide and rucaparib or enzalutamide and placebo, with androgen deprivation therapy if applicable. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 3 months for 2 years, then every 6 months for 3 years.

5 years

Treatment Details

Interventions

  • Enzalutamide
  • Rucaparib camsylate
Trial OverviewThe trial tests if adding Rucaparib (a PARP inhibitor) to Enzalutamide improves outcomes in men whose prostate cancer has spread and resists hormone therapy. It's a phase III study where patients are randomly assigned either the combination of both drugs or Enzalutamide alone, plus placebos as needed.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I (enzalutamide, rucaparib)Experimental Treatment7 Interventions
Patients receive enzalutamide PO QD and rucaparib PO BID. Patients who did not undergo bilateral orchiectomy also receive ADT consisting of leuprolide acetate IM, goserelin acetate SC every 12 weeks or degarelix SC. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group II: Arm II (enzalutamide, placebo)Active Control6 Interventions
Patients receive enzalutamide PO QD and placebo PO BID. Patients who did not undergo bilateral orchiectomy also receive ADT consisting of leuprolide acetate IM, goserelin acetate SC every 12 weeks or degarelix SC. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Enzalutamide is already approved in United States, European Union, Canada, Japan for the following indications:

🇺🇸
Approved in United States as Xtandi for:
  • Metastatic castration-resistant prostate cancer (mCRPC)
  • Non-metastatic castration-resistant prostate cancer (nmCRPC)
🇪🇺
Approved in European Union as Xtandi for:
  • Metastatic castration-resistant prostate cancer (mCRPC)
  • Non-metastatic castration-resistant prostate cancer (nmCRPC)
🇨🇦
Approved in Canada as Xtandi for:
  • Metastatic castration-resistant prostate cancer (mCRPC)
  • Non-metastatic castration-resistant prostate cancer (nmCRPC)
🇯🇵
Approved in Japan as Xtandi for:
  • Metastatic castration-resistant prostate cancer (mCRPC)
  • Non-metastatic castration-resistant prostate cancer (nmCRPC)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials
521
Recruited
224,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a phase 2 study involving 60 patients with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide treatment led to a significant decline in prostate-specific antigen (PSA) levels in 45% of patients, indicating its efficacy in managing this advanced cancer.
The study found that the presence of the androgen receptor variant ARV7 was linked to primary resistance to enzalutamide, suggesting that certain androgen signaling characteristics before treatment can predict patient response to the drug.
Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer.Efstathiou, E., Titus, M., Wen, S., et al.[2022]
Enzalutamide significantly improved radiographic progression-free survival (rPFS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer across various disease subgroups, including nonvisceral and visceral disease, as well as low- and high-volume bone disease.
The treatment was well tolerated, showing clinically significant benefits in overall survival (OS) for most subgroups, although the results were less definitive for patients with visceral disease.
The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer.Evans, CP., Higano, CS., Keane, T., et al.[2022]
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.
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]

References

Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. [2022]
The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. [2022]
Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. [2022]
Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN. [2022]
Eyeing Enzalutamide for Hormone-Sensitive Prostate Cancer. [2020]
Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]
A European, prospective, observational study of enzalutamide in patients with metastatic castration-resistant prostate cancer: PREMISE. [2022]
Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. [2022]
A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. [2023]
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]
11.United Statespubmed.ncbi.nlm.nih.gov
Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. [2021]