Rucaparib Camsylate in Treating Patients with Metastatic or Biochemically Recurrent Prostate Cancer

Inclusion Criteria

• Willing and able to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for the release of personal health information. * NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Histological or cytologic proof of adenocarcinoma of the prostate.
• Pathogenic mutation in one or more homologous recombination deoxyribonucleic acid (DNA)-repair genes (BRCA1, BRCA2, ATM, CHEK2, NBN, BRIP1, RAD50, RAD51C, RAD51D, PALB2, MRE11, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM) as documented by a clinical Clinical Laboratory Improvement Act (CLIA)-grade, saliva, tissue or blood-based (i.e leukocyte DNA) genetic or molecular test (including but not limited to Invitae, Foundation One, Color Genomics, etc). Germline and/or molecular testing will not be offered as an eligibility screen.
• All patients must be ineligible for or have declined androgen deprivation therapy (ADT)-based systemic treatment, if indicated.
• Absolute PSA >= 2.0 ng/ml at screening.
• Either (1) Metastatic disease as defined for one or more bone metastases confirmed by bone scintigraphy or radiographic soft tissue metastasis by computed tomography (CT) and/or bone scan, performed within 8 weeks. Or (2) biochemically recurrence disease as defined by a prostate specific antigen (PSA) > 0.2 ng/ml post prostatectomy or a PSA rise of 2 ng/ml or more from the nadir after radiation therapy.
• Serum testosterone >= 100 ng/dl.
• Hemoglobin >= 10.0 g/dL with no blood transfusion in the past 28 days (within 28 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 28 days prior to administration of study treatment)
• Platelet count >= 100 x 10^9/L (within 28 days prior to administration of study treatment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 3.0 x institutional upper limit of normal (within 28 days prior to administration of study treatment) * Note: Patients with elevations in bilirubin, AST, or ALT should be thoroughly evaluated for the etiology of this abnormality prior to entry and patients with evidence of viral infection should be excluded.
• Participants must have creatinine clearance estimated using the Cockcroft-Gault equation of >= 51 mL/min (within 28 days prior to administration of study treatment) * Note: Patients with creatinine clearance between 51- 80 mL/min either at trial enrolment or during the course of the trial should be monitored every 2 weeks for laboratory assessment and toxicity evaluation.
• Eastern Cooperative Oncology Group (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, 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 treatment with anti-androgens (e.g., bicalutamide, nilutamide, enzalutamide, apalutamide) or androgen synthesis inhibitors (e.g., abiraterone, orteronel) at therapeutic dosing for more than one month within the past 6 months is not permitted. If used for less than one month, the subject may be enrolled. The use of 5-alpha reductase inhibitor therapy (e.g., finasteride, dutasteride) is allowed, as long as the subject has been on a steady dose of the medication for the past 6 months and has tolerated it satisfactorily.
• Presence of visceral (i.e. lung or liver) metastases > 3 cm in long-axis dimension.
• Pain due to bone metastases requiring narcotic analgesics.
• Prior treatment with intravenous chemotherapy.
• Use of any prohibited concomitant medications 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 electrocardiography (ECG) with corrected QT interval (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 human immunodeficiency virus (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.