Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations

Inclusion Criteria:

Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
Males aged 18 years of age and above
Histological or cytologic proof of adenocarcinoma of the prostate
Germline mutation in one or more homologous recombination DNA-repair genes (BRCA1, BRCA2, ATM, CHEK2, NBN, RAD50, RAD51C, RAD51D, PALB2, MRE11, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM) as documented by a clinical CLIA-grade, genetic test (including but not limited to Invitae, Color Genomics, etc)
All patients must be ineligible for or have declined androgen deprivation therapy (ADT)-based systemic treatment
Absolute PSA ≥2.0 ng/ml at screening.
Radiographic evidence of metastatic disease by CT scan and bone scan, performed within the prior 8 weeks.
Serum testosterone ≥ 100 ng/dl.

Participants 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 with no blood transfusion in the past 28 days
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))

Participants 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
ECOG Performance Status <2
Participants must have a life expectancy ≥ 12 months.
Male participants and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination [see appendix E for acceptable methods], throughout the period of taking study treatment and for 6 months after last dose of study drug to prevent pregnancy in a partner.

Exclusion Criteria:

Current active second malignancy (history of non-melanoma skin cancers and superficial bladder cancers are allowed)
Prior ADT in the past 6 months. Prior ADT in context of neoadjuvant/adjuvant primary is allowed; prior ADT for biochemical recurrence is also allowed, as long as no ADT has been administered in past 6 months and testosterone has recovered (>100 ng/dl). The total duration of prior ADT should not exceed 24 months.
Prior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) in the past 6 months is not permitted. 5-alpha reductase inhibitor therapy (e.g. finasteride, dutasteride) is allowed, as long as subject has been stable on medication for past 6 months.
Presence of visceral (i.e. lung or liver) metastases >3cm in long-axis dimension.
Pain due to bone metastases requiring narcotic analgesics.
Prior treatment with intravenous chemotherapy.
Use of any prohibited concomitant medications (Appendix B: Medications With the Potential for Drug-Drug Interactions) within the prior 2 weeks.
Involvement in the planning and/or conduct of the study (applies to both Clovis Oncology staff and/or staff at the study site)
Previous enrollment in the present study
Participation in another clinical study with an investigational product during the last 1 month.
Any previous treatment with a PARP inhibitor, including rucaparib.
Resting ECG with QTc > 480 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
Major surgery within 2 weeks of starting study treatment, and patients must have recovered from any effects of any major surgery.
Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 6 months) myocardial infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung disease, or any psychiatric disorder that prohibits obtaining informed consent.
Unable to swallow orally administered medication or gastrointestinal disorders likely to interfere with absorption of the study medication.
Immunocompromised patients, e.g., patients who are known to be serologically positive for HIV. Known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
Known hypersensitivity to rucaparib or any of the excipients of the product.
Whole blood transfusions in the last 30 days prior to entry to the study.