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

Prior treatment

• 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.
• 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.
• 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.
• Major surgery within 2 weeks of starting study treatment, and patients must have recovered from any effects of any major surgery.
• Whole blood transfusions in the last 30 days prior to entry to the study.

Other illness

• Current active second malignancy (history of non-melanoma skin cancers and superficial bladder cancers are allowed)
• 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.
• 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.

Lab values

• Resting ECG with QTc \> 480 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome

Other

• Presence of visceral (i.e. lung or liver) metastases \>3cm in long-axis dimension.
• Pain due to bone metastases requiring narcotic analgesics.
• Involvement in the planning and/or conduct of the study (applies to both Clovis Oncology staff and/or staff at the study site)

• 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.