Carboplatin or Olaparib for BRcA Deficient Prostate Cancer

Launched by VA OFFICE OF RESEARCH AND DEVELOPMENT · Jul 29, 2019

Keywords

ClinConnect Summary

This clinical trial is studying two different treatments for men with advanced prostate cancer that has become resistant to hormone therapy. The goal is to see which treatment works better: a chemotherapy drug called carboplatin or a targeted therapy called olaparib. Both treatments are given to patients whose tumors have specific genetic mutations. Participants will first receive one of the treatments and, if their cancer progresses, they will switch to the other treatment. Throughout the trial, doctors will monitor the safety and effectiveness of the treatments using various tests.

To be eligible for this trial, participants must be men over 18 years old with a diagnosis of prostate cancer and specific genetic mutations related to their condition. They should be undergoing hormone therapy and have certain health criteria, like good organ function. If someone joins the trial, they can expect to receive either treatment every few weeks and will have regular check-ups to assess how well the treatment is working. This trial is currently recruiting participants, so if you meet the criteria and are interested, you might want to talk to your doctor about it.

Gender

MALE

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 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.