Carboplatin or Olaparib for BRcA Deficient Prostate Cancer

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-gradeneuroendocrine 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 anorchiectomy must be maintained on effective GnRH analogue/antagonist therapy

5. mCRPC as defined by serum testosterone < 50 ng/ml (for patients on GnRH analogues orantagonists) and at least one of the following:

• PSA level of at least 2 ng/ml that has risen on at least 2 successive occasionsat least 1 week apart

• Evaluable disease progression by modified RECIST 1.1 (Response EvaluationCriteria in Solid Tumors)

• Progression of metastatic bone disease on bone scan, CT or MRI with > 2 newlesions

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, whichconfirms RAD51B, RAD51C, RAD51D, or RAD54L mutations (see Introduction, Section 2for study design and previous research on targeted therapy) from primary, metastatictumor or circulating tumor DNA, or pathogenic/likely pathogenic germline variant asassessed by a CLIA certified laboratory level assay for DNA sequencing.

9. Patients must have normal organ and bone marrow function measured within 28 daysprior 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 arepresent in which case, they must be < 5x ULN

• Patients must have creatinine clearance estimated using the Cockcroft-Gaultequation of >51 mL/min: Estimated creatinine clearance =(140-age [years]) xweight (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 - immunohistochemicalevidence of neuroendocrine differentiation without morphologic evidence is notexclusionary)

4. Prior treatment with platinum, mitoxantrone or PARP inhibitor for castrationresistant prostate cancer

5. Known parenchymal brain metastasis

6. Active or symptomatic viral hepatitis or chronic liver disease AST or ALT > 2.5 xULN or total bilirubin > ULN (unless Gilbert's syndrome is the etiology ofhyperbilirubinemia)

7. Subjects with myelodysplastic syndrome/acute myeloid leukemia or with featuressuggestive 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 requiredwashout 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) ormoderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washoutperiod prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for otheragents

10. Subjects unable to swallow orally administered medication and subjects withgastrointestinal disorders likely to interfere with absorption of the studymedication

11. Clinically significant heart disease as evidenced by myocardial infarction, orarterial thrombotic events in the past 6 months, severe or unstable angina, or NewYork Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fractionmeasurement 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 limitingcompliance with study requirements or understanding HIPAA authorization and/orgiving 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.