PLATI-PARP: A Phase 2 Study of Induction Docetaxel and Carboplatin followed by Maintenance Rucaparib in Treatment of Patients with Metastatic Castration Resistant Prostate Cancer with Homologous Recombination DNA Repair Deficiency
Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
Histologically or cytologically confirmed adenocarcinoma of the prostate (excluding predominant small cell histology)
Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
Castration resistant prostate cancer as defined by serum testosterone
Presence of metastatic disease on bone or computed tomography (CT) scan
?Evaluable disease progression by modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)
?Bone disease on bone scan
Prior therapy with sipuleucel-T, abiraterone, enzalutamide, docetaxel, and/or cabazitaxel; there is no limit to the number of prior treatment regimens, so long as prior therapy does not include platinum chemotherapy or a PARP inhibitor
Eastern Cooperative Oncology Group (ECOG) performance status of =
Life expectancy >= 12 weeks
No prior malignancy is allowed except:
?Adequately treated basal cell or squamous cell skin cancer or
?In situ carcinoma of any site or
?Other adequately treated malignancy for which the patient has been disease-free for at least one year (any prior chemotherapy is allowed)
Documented evidence of at least ONE or MORE of the following:
?Biallelic inactivation of genes involved in homologous recombination repair in the tumor
?Biallelic inactivation of other genes involved in homologous DNA recombination repair in the tumor may be included at investigator's discretion
?Homologous recombination repair deficiency by genomic signature in the tumor
?Clearly pathogenic or likely pathogenic germline mutation in BRCA2, BRCA1 and/or ATM
?(Note: the following are not alone sufficient for eligibility and require additional criteria to be met: germline variant of uncertain significance in BRCA1, BRCA2 and/or ATM; germline mutations in other HR genes)
Within 14 days of first dose of study drug: Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
Within 14 days of first dose of study drug: Platelets > 100 x 10^9/L
Within 14 days of first dose of study drug: Hemoglobin >= 9 g/dL
Within 14 days of first dose of study drug: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =
Within 14 days of first dose of study drug: Bilirubin =
Within 14 days of first dose of study drug: Serum creatinine == 45 mL/min using the Cockcroft Gault formula
Other eligibility criteria may apply.
Currently receiving active therapy for other neoplastic disorders
Symptomatic and/or untreated central nervous system (CNS) metastases; patients with asymptomatic previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, active or symptomatic viral hepatitis or chronic liver disease
Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class II-IV heart disease or cardiac ejection fraction measurement of
Treatment with an investigational therapeutic drug within 30 days of cycle 1
Prior therapy with a PARP inhibitor (e.g., olaparib, talazoparib, veliparib, niraparib, rucaparib)
Prior therapy with a platinum chemotherapy (e.g. cisplatin, carboplatin, oxaliplatin)
Active, ongoing toxicity (Common Terminology Criteria for Adverse Events [CTCAE] grade 2 or higher) from prior therapy
Presence of dementia, psychiatric illness, and/or social situations limiting compliance with study requirements or understanding and/or giving of informed consent
Pre-existing duodenal stent and/ or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
Any condition(s), medical or otherwise, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained
Other exclusion criteria may apply.