Hispanic/Latino and Non-Hispanic BlAck Patients Treated With niRaparib and Abiraterone Acetate Plus Prednisone for Metastatic hOrmone Sensitive Prostate Cancer With Deleterious Homologous recombinatioN Repair Alterations: a Phase II, Open Label studY
This is an open label, phase II trial in subjects with treatment naïve, metastatic hormone sensitive prostate cancer (mHSPC) with deleterious homologous recombination repair (HRR) alteration(s). These include pathologic alterations in BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L. A total of 64 people will be enrolled to the study.
• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• ≥ 18 years of age at the time of consent.
• Self-identify as Hispanic/Latino or non-Hispanic black racial/ethnic background.
• ECOG Performance Status of ≤ 2 within 30 days prior to registration.
• Histologically confirmed diagnosis of prostate adenocarcinoma.
• Deleterious HRR alteration(s) per any validated test, next generation sequencing (NGS) mutational analysis (tissue or liquid). These include BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L.
• Radiographic evidence of metastatic disease as per conventional CT or MRI of chest, abdomen pelvis and bone scan, according to RECIST version 1.1 criteria in subjects with measurable disease and PCWG3 criteria for subjects with bone only disease (1, 2). Evidence of metastatic disease detected on Axumin or PSMA PET/CT will need confirmation on conventional CT or MRI/bone scans.
• Hormone sensitive, treatment naïve/minimally treated \[first generation androgen receptor inhibitor (ARI) such as bicalutamide ≤ 45 days, ADT ± abiraterone acetate plus prednisone ≤ 45 days allowed\]. Prior therapy for localized prostate cancer allowed (including but not limited to radiation therapy, prostatectomy, lymph node dissection ± ADT, must have been completed \> 6 months prior to registration).
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 30 days prior to registration.
‣ Platelets (Plt): ≥ 100 x 10\^9/L (Independent of transfusions for at least 28 days prior to registration)
⁃ Absolute Neutrophil Count (ANC): ≥ 1.5 x 10\^9/L (Independent of hematopoietic growth factors for at least 28 days prior to registration)
⁃ Hemoglobin (Hgb): ≥ 9 g/dL (Independent of transfusions for at least 28 days prior to registration)
⁃ Creatinine: Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min
⁃ Total bilirubin: ≤ 1.5 × ULN or direct bilirubin ≤ 1 x ULN (For subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤1.5 × ULN, subjects may be eligible.)
⁃ Aspartate aminotransferase (AST): ≤ 3 × ULN
⁃ Alanine aminotransferase (ALT): ≤ 3 × ULN
⁃ Serum potassium: ≥ 3.5 mmol/L
⁃ Males able to father a child who are sexually active with a female of childbearing potential must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception.
⁃ Able to swallow the study medication tablets whole.
⁃ Life expectancy ≥ 12 months.
⁃ As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.