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Clinical Trial 18986

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

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

  • Jingsong Zhang

Call 813-745-6100
or 1-800-679-0775
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 line of 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.
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or history of chronic hepatitis B or C, with the exception of patients with sustained virologic response after completion of treatment for hepatitis C.
  • Received treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs within > Adverse effect of prior therapy not resolved to CTCAE Grade 1 or below with the exception of alopecia. Ongoing Grade 2 non-hematologic toxicity related to most recent treatment regimen may be permitted with prior advanced approval from the sponsor.
  • Initiated low-dose corticosteroid, denosumab, or bisphosphonate therapy or adjusted low-dose corticosteroid, denosumab, or bisphosphonate dose/regimen within > Non-study related minor surgical procedure within > Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for entry into the study.
  • Additional criteria may apply