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


Condition: ATM Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation, Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Homologous Recombination Deficiency, Prostate Carcinoma Metastatic in the Bone, PSA Level Greater Than or Equal to Two, PSA Progression, Stage IV Prostate Adenocarcinoma AJCC v7

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03442556

Sponsor: University of Washington

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • 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 < 50 ng/ml and PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
  • 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 in the castration resistant setting, so long as prior therapy does not include platinum chemotherapy or a PARP inhibitor; prior platinum chemotherapy in the hormone sensitive setting is permitted, so long as it has been at least 6 months since last dose
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
  • 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: * Pathogenic mutation or inactivating alteration of a gene involved in homologous recombination repair in the tumor
  • Note, that if this alteration is identified in a circulating tumor deoxyribonucleic acid (ctDNA) assay, the variant-allele fraction must be > 20% to indicate relevance to predominant tumor clone
  • Mutation in one or more 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 by BROCA-HR, Foundation One or equivalent assay
  • Presence of pathogenic or likely pathogenic germline mutation/variant in BRCA2, BRCA1, ATM or PALB2
  • Note: Germline mutations in other HR genes will be considered at investigator's discretion)
  • 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) =< 3 x ULN; if liver metastases, then =< 5 x ULN (within 14 days of first dose of study drug)
  • Bilirubin =< 1.5 x ULN (< 2 x ULN if hyperbilirubinemia is due to Gilbert's syndrome) (within 14 days of first dose of study drug)
  • Serum creatinine =< 1.5 x ULN or estimated glomerular filtration rate (GFR) >= 45 mL/min using the Cockcroft Gault formula (within 14 days of first dose of study drug)

Exclusion Criteria:

  • 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 < 35 % at baseline
  • 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) in the castration resistant setting; (prior platinum chemotherapy in the hormone sensitive setting is permitted, so long as time since last dose is 6 months or greater)
  • 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

View trial on ClinicalTrials.gov