Clinical Trial 18986

Cancer Type: Genitourinary
Interventions:AG-014447 (Rucaparib); CO-338 (Rucaparib); PF-01367338-BW (Rucaparib); Rucaparib

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Jingsong Zhang

Overview

Study Title

TRITON2: A Multicenter, Open-label Phase 2 Study of Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer Associated with Homologous Recombination Deficiency.

Summary

The purpose of this study is to determine how patients with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib.

Objective

Primary Objective: - To assess the efficacy of rucaparib based on the response rate in mCRPC patients with HRD who progressed on AR-targeted therapy (abiraterone acetate, enzalutamide, or investigational AR-targeted agent) and taxane-based chemotherapy in the castrationresistant setting Secondary Objectives: - To assess duration of response (DOR). - To assess radiologic PFS (rPFS). - To assess overall survival (OS). - To assess clinical benefit rate (CBR). - To assess PSA response >/= 50% (all participants). - To assess PSA response >/= 90% (all participants). - To assess time to PSA progression. - To characterize the steady-state pharmacokinetics (PK) of rucaparib in mCRPC patients. - To assess safety and tolerability. Exploratory Objectives: - To assess response in circulating tumor cells (CTCs). - To evaluate Patient-reported Outcome (PRO) using the EuroQol 5 dimensions questionnaire (EQ-5D), Functional Assessment of Cancer Therapy - Prostate (FACTP), analgesic drug score, and Brief Pain Inventory - Short Form (BPI-SF) instruments. - To assess changes in the molecular profile over time of matched pre and post-treatment tumor or plasma samples. - To assess concordance in HR gene mutation status in matched screening biopsy tissue, archival primary tumor tissue and plasma circulating tumor DNA (ctDNA). - To assess ctDNA as a molecular marker of response. - To assess CTC phenotype as a marker of response. - To assess time to first subsequent antineoplastic therapy. - To evaluate loss of heterozygosity (LOH) in metastatic disease site biopsy and archival primary tumor tissue samples. - To evaluate mechanisms of response and resistance in ctDNA and progression tumor tissue samples.

Inclusion Criteria

  • Be 18 years old at the time the informed consent form is signed
  • Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate
  • Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM)
  • Experienced disease progression after having received at least 1 but no more than 2 prior next-generation androgen receptor-targeted therapies, and 1 prior taxane-based chemotherapy, for castration-resistant disease
  • Have a deleterious mutation in BRCA1/2 or ATM, or molecular evidence of other homologous recombination deficiency
  • Additional criteria may apply

  • Exclusion Criteria

  • Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
  • Prior treatment with any PARP inhibitor, mitoxantrone, cyclophosphamide or any platinum-based chemotherapy
  • Symptomatic and/or untreated central nervous system metastases
  • Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of rucaparib
  • Additional criteria may apply