Rucaparib Camsylate and Nivolumab in Treating Patients with Metastatic Castration-Resistant Prostate Cancer or Advanced or Recurrent Endometrial Cancer

Inclusion Criteria

• Patients must have the ability to understand and the willingness to sign a written informed consent document
• Patients must have histologically or cytologically confirmed castration-resistant prostate cancer (CRPC) or endometrial cancer that is metastatic. Evidence of disease progression on a prior therapy is not required
• Patients must have at least one lesion that is amenable to biopsy and the treating physician must deem this safe
• Patient must be willing to undergo two mandatory research-only biopsies
• For prostate cancer patients: subjects must be surgically or medically castrated, with serum testosterone levels =< 50 ng/mL. Patients being treated with gonadotropin-releasing hormone (GnRH) agonists must have such therapy continued throughout the study
• Prostate cancer patients: Patients should have received at least one androgen-receptor (AR)-targeted therapy with abiraterone acetate or enzalutamide. Multiple lines of prior therapy except as noted below are permitted. A washout of two weeks from prior endocrine therapy (other than GnRH agonist); four weeks washout period from prior cytotoxic chemotherapy or other anticancer agents is required (prior to day 1 of study therapy); six weeks washout period to allow for anti-androgen withdrawal for patients managed with bicalutamide
• Endometrial cancer patients: An unlimited number of prior hormonal and/or chemotherapy regimens are permitted. A washout of two weeks from prior endocrine therapy (other than GnRH agonist) and four weeks from prior cytotoxic chemotherapy or other anticancer agents is required (prior to day 1 of study therapy)
• At least 5 days should have elapsed since any non-study related minor surgical procedure and at least 21 days since any major surgical procedure prior to the first dose of rucaparib and the first dose of nivolumab
• Must have an ability to swallow pills or capsules. Patients should have no current clinical evidence of bowel obstruction
• Eastern Cooperative Oncology Group (ECOG) performance status must be =< 1
• Hemoglobin >= 10 g/dL (without transfusion in the last 4 weeks)
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 1.5 x institutional upper limit of normal
• Creatinine =< 1.5 x institutional upper limit of normal OR
• Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Patients must have a serum albumin > 2.5
• Prior palliative radiotherapy must have been completed at least 2 weeks prior to first dose of study drug. Subjects with symptomatic tumor lesions at baseline that may require palliative radiotherapy within 4 weeks of first dose of study drug are strongly encouraged to receive palliative radiotherapy prior to enrollment
• Rucaparib caused post-implantation loss (100% early resorptions) at all doses administered in an embryo-fetal development study. Based on its mechanism of action, nivolumab can cause fetal harm when administered to a pregnant woman. Pregnant women are therefore not eligible for this study * Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test result less than 3 days prior to administration of the first dose of rucaparib * WOCBP must not be considering getting pregnant during the study * WOCBP and their male partners must agree to use a highly effective, reliable form of contraception during treatment; for 6 months following the last dose of rucaparib; and for at least 5 months following the last dose of nivolumab * Men who are sexually active with WOCBP must agree to use a highly effective, reliable form of contraception during treatment; 6 months following the last dose of rucaparib; and for a period of 7 months after the last dose of nivolumab * In addition to the above methods of contraception, use of a condom by male patients is recommended to prevent transfer of drug through semen

Exclusion Criteria

• Patients with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes, mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, childhood asthma that is not currently active, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease * Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study drug is permitted
• Patients who are receiving any other investigational agents
• Prior exposure to PD-1 or PD-L1 inhibitors, other immune checkpoint inhibitors (e.g. anti-LAG-3, and anti-CTLA-4 antibodies), or PARP inhibitors
• Prior exposure to Ra223 or other systemic radionuclides
• Patients with a “currently active” second invasive malignancy other than non-melanoma skin cancers. Patients are not considered to have a “currently active” malignancy if they have completed therapy and have been free of disease for >= 1 years
• Patients with known and untreated or progressing brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events * Patients whose brain metastases have been treated with surgery and/or radiotherapy and are without evidence of progression on scan for at least 4 weeks, and are off steroids or antiseizure medications, will be eligible
• Patients with symptomatic or impending spinal cord compression are not eligible unless appropriately treated
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or rucaparib
• Patients on parenteral nutrition are not eligible. Patients must not have a pre-existing duodenal stent or any gastrointestinal disorder or defect that would, in the opinion of the treating investigator, interfere with absorption of rucaparib
• Uncontrolled intercurrent illness including, but not limited to, requirement for oxygen therapy, ongoing or active infection other than minor urinary tract infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Known history of chronic hepatitis B or C as evidenced by: * Positive test for hepatitis B surface antigen * Positive test for qualitative hepatitis C viral load (by polymerase chain reaction [PCR]) ** Note: Subjects with positive hepatitis C antibody and negative quantitative hepatitis C by PCR are eligible
• Human Immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with rucaparib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
• Prior organ allograft or allogeneic bone marrow transplantation
• Adverse effect of prior therapy not improved to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or below with the exception of alopecia. Ongoing grade 2 non-hematologic toxicity (e.g. neuropathy) related to most recent treatment regimen may be permitted with prior advanced approval from the lead principal investigator
• Initiated denosumab or bisphosphonate therapy or adjusted denosumab or bisphosphonate dose/regimen within 4 weeks prior to first dose of rucaparib. Patients on a stable denosumab or bisphosphonate regimen are eligible and may continue treatment
• Evidence or history of active or latent tuberculosis infection including purified protein derivative (PPD) recently converted to positive
• Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 12 weeks prior to study drug. The use of inactivated seasonal influenza vaccines, e.g., Fluzone, will be permitted on study without restriction
• Endometrial cancer patients who may require pelvic radiation to address vaginal bleeding should have such treatment prior to enrolling on the study