RecruitingPhase 2

Carboplatin or Olaparib for BRcA Deficient Prostate Cancer

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
Male only
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: MRI scans

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study compares carboplatin chemotherapy with olaparib for prostate cancer that has spread and keeps growing despite treatment to lower testosterone. It is for people with certain gene changes. Patients are assigned by chance to start one drug and may switch to the other if their cancer gets worse.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Sign forms agreeing to join the study and allowing use of your health information.
  • Have prostate cancer that has spread and is getting worse despite very low testosterone, shown by blood tests or scans.
  • Continue treatment to lower testosterone, unless you have had surgery to remove the testicles.
  • Have already received abiraterone, enzalutamide, apalutamide, or darolutamide.
  • Be able to do daily self-care and at least light activities.
  • Have DNA testing that confirms a change in RAD51B, RAD51C, RAD51D, or RAD54L. The detailed entry rules list these four genes.
  • Have blood cell counts and liver and kidney test results that meet study limits, checked within 28 days before treatment.

Who can't join

  • Have small-cell prostate cancer or a pure high-grade neuroendocrine type; receive active treatment for another cancer; or have known cancer spread into brain tissue.
  • Have already received platinum chemotherapy, mitoxantrone, or a PARP inhibitor for prostate cancer that resists testosterone-lowering treatment.
  • Be in another study testing a drug or device, or have received an experimental treatment within 30 days before starting this study.
  • Have active or symptomatic viral hepatitis, certain long-term liver problems, or MDS or AML—serious bone marrow or blood disorders—or signs of these disorders.
  • Take certain medicines or supplements that affect how olaparib works. These require a break of 2 to 5 weeks before starting olaparib, depending on the medicine.
  • Be unable to swallow pills, or have digestive problems that could keep your body from absorbing the study drug.
  • Have serious heart disease, including a recent heart attack or artery blood clot, severe or unstable chest pain, or weak heart pumping.
  • Have memory, mental health, social, or other problems that prevent informed consent or following study rules, or that the study doctor believes could make participation unsafe or harm study results.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: 1. Signed study informed consent form (ICF) and HIPAA authorization form 2. Diagnosis of prostate cancer (pure small-cell histology or pure high-grade neuroendocrine histology are excluded; neuroendocrine differentiation is allowed) 3. 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 4. mCRPC as defined by serum testosterone \< 50 nanograms per milliliter (ng/ml) for patients on GnRH analogues or antagonists) and at least one of the following: * Prostate-specific antigen (PSA) level of at least 2 nanograms per milliliter (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 5. Prior therapy with abiraterone acetate, enzalutamide, apalutamide, or darolutamide 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of \< 2 (see Appendix 3, ECOG Grading Scale) 7. 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. 8. 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 grams per deciliter (g/dL) * Absolute neutrophil count (ANC) \> 1.5 x 109/liter (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

Study sites (18)

CA

CO

DC

FL

GA

ID

IL

MI

MN

MO

NC

NY

OR

PA

WA

WI