100 Participants Needed

Carboplatin vs Olaparib for Prostate Cancer

(COBRA Trial)

Recruiting at 18 trial locations
RB
ML
Overseen ByMakayla L DeJong, BA
Age: 18+
Sex: Male
Trial Phase: Phase 2
Sponsor: VA Office of Research and Development
Must be taking: GnRH analogues
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human 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

MJ

Maneesh Jain, MD

Principal Investigator

Washington DC VA Medical Center, Washington, DC

PT

Phoebe Tsao, MD MSc

Principal Investigator

VA Ann Arbor Healthcare System, Ann Arbor, MI

RB

Robert B Montgomery, MD

Principal Investigator

VA Puget Sound Health Care System Seattle Division, Seattle, WA

RB

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

Absolute neutrophil count (ANC) > 1.5 x 109/L
Platelet count > 100 x 109/L
My prostate cancer is resistant to medical or surgical treatments to lower testosterone.
See 15 more

Exclusion Criteria

Any condition(s), medical or otherwise, which, in the opinion of the Investigators, would jeopardize either the patient or the integrity of the data obtained.
I am currently undergoing treatment for another cancer.
Concurrent enrollment in another clinical investigational drug or device study
See 11 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

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

Varies until progression or intolerance
Every 21 days for carboplatin, daily for olaparib

Crossover to Second-line Treatment

Participants switch to the opposite study medication (carboplatin or olaparib) after first progression, receiving treatment until intolerance or progression

Varies until progression or intolerance
Every 21 days for carboplatin, daily for olaparib

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
End of treatment visit 28 days after completion or withdrawal

Treatment Details

Interventions

  • Carboplatin
  • Olaparib
Trial OverviewThe trial compares carboplatin chemotherapy to olaparib pills for men with a type of advanced prostate cancer. Patients are randomly chosen to start with one drug and can switch to the other if the first one stops working. The study checks how well each drug controls the cancer.
Participant Groups
2Treatment groups
Active Control
Group I: Treatment Arm 2 - Olaparib to CarboplatinActive Control2 Interventions
Participants are prescribed olaparib which is taken orally at home, twice daily, 300 mg in 28 day cycles, as first line therapy. For second line (crossover), carboplatin is administered AUC 5 IV every 21 days thereafter.
Group II: Treatment Arm 1 - Carboplatin to OlaparibActive Control2 Interventions
Participants are administered carboplatin AUC 5 IV first, which is administered Cycle-1, Day-1, and then every 21 days as first line therapy. For second line (crossover), olaparib is prescribed and taken orally at home, twice daily, 300 mg in 28 day cycles.

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

🇺🇸
Approved in United States as Paraplatin for:
  • Ovarian cancer
  • Testicular cancer
  • Lung cancer
  • Head and neck cancer
  • Brain cancer
🇪🇺
Approved in European Union as Carboplatin for:
  • Ovarian cancer
  • Small cell lung cancer
🇨🇦
Approved in Canada as Carboplatin for:
  • 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

Trials
1,691
Recruited
3,759,000+

Findings from Research

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.
The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety.Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]
The OPINION study is evaluating the safety and efficacy of olaparib as a maintenance therapy for women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer who do not have BRCA mutations, involving patients who have undergone at least two prior lines of platinum-based chemotherapy.
The primary goal of the study is to assess progression-free survival, which will help determine how effective olaparib is in delaying cancer progression in this specific patient population.
Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design.Poveda, AM., Davidson, R., Blakeley, C., et al.[2020]
Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.
This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.
New Adjuvant Treatment for High-Risk Early Breast Cancer.Aschenbrenner, DS.[2022]

References

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]
Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]
New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]
A Phase I Study of Combination Olaparib and Radium-223 in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) with Bone Metastases (COMRADE). [2023]
Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. [2022]
Olaparib: first global approval. [2020]
Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer. [2019]