No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
Prior Safety Data
This treatment has already been tested in at least one earlier human trial.
Ready to participate?
Review the details below, then apply to join this clinical trial.
At a Glance
Age
18 and older
Sex
Male
Trial phase
Phase 2
Study type
Interventional
Purpose
Health Services Research
Participants needed
100 (estimated)
Sponsor
VA Office of Research and Development · Federal
Who this trial is looking for
This trial is looking for men with a specific type of prostate cancer that has spread and is resistant to hormone therapy. Participants will receive either carboplatin or olaparib as their initial treatment, with the option to switch medications if their condition worsens.
Are You a Good Fit for This Trial?
Must be takingGnRH analoguesGonadotropin-releasing hormone antagonists
You may be able to join if
I am a man over 18 years old.
I have been diagnosed with prostate cancer.
I am on ongoing hormone therapy.
I have metastatic castrate resistant prostate cancer.
I have certain genetic mutations confirmed by testing.
I have normal organ and bone marrow function.
I have previously used specific hormone therapy treatments.
I can provide signed consent to join the trial.
You may not be able to join if
I am currently receiving treatment for other cancers.
I have a history of small cell carcinoma.
I have received certain prior treatments for my prostate cancer.
I have known brain metastases.
I have significant liver disease.
I have a heart condition that affects me significantly.
I can't swallow oral medications.
I have a psychiatric condition that affects my understanding.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer a few quick questions to see if you may meet the eligibility requirements.
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, BR…
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.
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Eligibility 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 and…
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.
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