Carboplatin vs Olaparib for Prostate Cancer
(COBRA Trial)
Trial Summary
What is the purpose of this trial?
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations. Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28 day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria. Participants then crossover from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you must stop all current medications. However, you must stop taking strong or moderate CYP3A inhibitors and inducers before starting olaparib. The washout period is 2 weeks for inhibitors and 3-5 weeks for inducers, depending on the specific medication.
What data supports the idea that Carboplatin vs Olaparib for Prostate Cancer is an effective drug?
The available research shows that Olaparib, when combined with another treatment called radium-223, has shown early clinical benefits for men with a specific type of prostate cancer that has spread to the bones. In a study, 58% of patients did not see their cancer worsen for at least 6 months. This suggests that Olaparib can be an effective part of a treatment plan for prostate cancer, especially when used with radium-223. However, there is no direct comparison with Carboplatin for prostate cancer in the provided data.12345
What safety data exists for Carboplatin and Olaparib in prostate cancer treatment?
The safety data for Olaparib in prostate cancer treatment includes findings from a Phase I study where Olaparib was combined with Radium-223 in men with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. The study identified dose-limiting toxicities such as cytopenias, fatigue, and nausea, with the most common treatment-related adverse events being fatigue (92%) and anemia (58%). The recommended phase 2 dose (RP2D) of Olaparib was established at 200 mg orally twice daily with Radium-223. No specific safety data for Carboplatin in prostate cancer was provided in the research.13456
Is the drug Carboplatin, Olaparib a promising treatment for prostate cancer?
The combination of Carboplatin and Olaparib shows promise as a treatment for prostate cancer. Olaparib, a drug that helps prevent cancer cells from repairing themselves, has shown early clinical benefits when used with other treatments. Although the studies mainly focus on other types of cancer, the combination has been safe and effective in trials, suggesting potential for prostate cancer treatment.12347
Research Team
Maneesh Jain, MD
Principal Investigator
Washington DC VA Medical Center, Washington, DC
Phoebe Tsao, MD MSc
Principal Investigator
VA Ann Arbor Healthcare System, Ann Arbor, MI
Robert B Montgomery, MD
Principal Investigator
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Ryan Burri, MD
Principal Investigator
Bay Pines VA Healthcare System, Pay Pines, FL
Eligibility Criteria
Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has specific gene mutations (like BRCA1/2). They must have ongoing hormone treatment, measurable disease progression, normal organ/bone marrow function, no brain metastasis or other cancers being treated, and not taken certain drugs before.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
First-line Treatment
Participants receive either carboplatin (IV) every 21 days or olaparib (oral) twice daily in 28-day cycles until intolerance, complete response, or progression
Crossover to Second-line Treatment
Participants switch to the opposite study medication (carboplatin or olaparib) after first progression, receiving treatment until intolerance or progression
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Carboplatin
- Olaparib
Carboplatin is already approved in United States, European Union, Canada for the following indications:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
- Ovarian cancer
- Small cell lung cancer
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find a Clinic Near You
Who Is Running the Clinical Trial?
VA Office of Research and Development
Lead Sponsor