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Comparing Carboplatin and Olaparib for Prostate Cancer with DNA Repair Mutations

An Open-label, Multicenter Phase II Study to Compare the Efficacy of Carboplatin as First-line Followed by Second-line Olaparib Versus Olaparib as First-line Followed by Second-line Carboplatin in the Treatment of Patients With Castration Resistant Prostate Cancer Containing Homologous Recombination Deficiency

PHASE2 · VA Office of Research and Development · NCT04038502

This study is testing whether carboplatin or olaparib works better for men with advanced prostate cancer who have certain DNA repair mutations.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment100 (estimated)
Ages18 Years and up
SexMale
SponsorVA Office of Research and Development (fed)
Drugs / interventionschemotherapy
Locations18 sites (West Los Angeles, California and 17 other locations)
Trial IDNCT04038502 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of two treatments, carboplatin and olaparib, for men with metastatic castrate resistant prostate cancer (mCRPC) who have specific DNA repair mutations. Participants will be randomly assigned to receive either carboplatin or olaparib as their initial therapy, with the option to switch to the other treatment upon disease progression. The study aims to determine which of the two drugs provides a better response in this patient population. The trial is designed to improve treatment options for patients with targeted DNA repair mutations.

Who should consider this trial

Good fit: Ideal candidates are men over 18 years old with metastatic castrate resistant prostate cancer and specific DNA repair mutations.

Not a fit: Patients with pure small-cell or high-grade neuroendocrine prostate cancer histology may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide more effective treatment options for patients with specific genetic mutations associated with prostate cancer.

How similar studies have performed: Other studies have shown promising results using similar approaches with DNA repair mutations in cancer treatment.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Signed study informed consent form (ICF) and HIPAA authorization form
2. Male age \> 18 years
3. Diagnosis of prostate cancer (pure small-cell histology or pure high-grade neuroendocrine histology are excluded; neuroendocrine differentiation is allowed)
4. Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
5. mCRPC as defined by serum testosterone \< 50 ng/ml (for patients on GnRH analogues or antagonists) and at least one of the following:

   * PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
   * Evaluable disease progression by modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)
   * Progression of metastatic bone disease on bone scan, CT or MRI with \> 2 new lesions
6. Prior therapy with abiraterone acetate, enzalutamide, apalutamide, or darolutamide
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of \< 2 (see Appendix 3, ECOG Grading Scale)
8. Results of previous standard DNA testing, or previous research testing, which confirms RAD51B, RAD51C, RAD51D, or RAD54L mutations (see Introduction, Section 2 for study design and previous research on targeted therapy) from primary, metastatic tumor or circulating tumor DNA, or pathogenic/likely pathogenic germline variant as assessed by a CLIA certified laboratory level assay for DNA sequencing.
9. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:

   * Hemoglobin \> 10.0 g/dL
   * Absolute neutrophil count (ANC) \> 1.5 x 109/L
   * Platelet count \> 100 x 109/L
   * Total bilirubin \< 1.5 x institutional upper limit of normal (ULN)
   * Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) \< 2.5 x institutional upper limit of normal unless liver metastases are present in which case, they must be \< 5x ULN
   * Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of \>51 mL/min: Estimated creatinine clearance =(140-age \[years\]) x weight (kg))/ (serum creatinine (mg/dL) x 72)

Exclusion Criteria:

1. Currently receiving active therapy for other neoplastic disorder(s)
2. Concurrent enrollment in another clinical investigational drug or device study
3. Histologic evidence of small cell carcinoma (morphology alone - immunohistochemical evidence of neuroendocrine differentiation without morphologic evidence is not exclusionary)
4. Prior treatment with platinum, mitoxantrone or PARP inhibitor for castration resistant prostate cancer
5. Known parenchymal brain metastasis
6. Active or symptomatic viral hepatitis or chronic liver disease AST or ALT \> 2.5 x ULN or total bilirubin \> ULN (unless Gilbert's syndrome is the etiology of hyperbilirubinemia)
7. Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML
8. Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks
9. Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents
10. Subjects unable to swallow orally administered medication and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication
11. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of \< 35 % at baseline
12. Treatment with an investigational therapeutic within 30 days of Cycle-1
13. Presence of dementia, psychiatric illness, and/or social situations limiting compliance with study requirements or understanding HIPAA authorization and/or giving of informed consent
14. 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.

Where this trial is running

West Los Angeles, California and 17 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Metastatic Castrate Resistant Prostate Cancer, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L Mutations, metastatic prostate cancer

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.