Clinical Trial 18963

Cancer Type: Genitourinary
Interventions:Abiraterone acetate; Enzalutamide; Olaparib (Lynparza); Zytiga (Abiraterone acetate); prednisone

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Jingsong Zhang

Overview

Study Title

A Phase III, Open Label, Randomized Study to Assess the Efficacy and Safety of Olaparib (Lynparza) Versus Enzalutamide or Abiraterone Acetate in Men with Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment with a New Hormonal Agent and Have Homologous Recombination Repair Gene Mutations (Profound)

Summary

This research study is designed to see if olaparib is effective in treating a certain type of prostate cancer with a defect in the way it repairs damage to DNA [mutation(s) in Homologous Recombination Repair (HRR) genes], how it compares to enzalutamide or abiraterone, and what side effects it may cause.

Objective

Primary Objective: To determine the efficacy (as assessed by rPFS) of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with mCRPC with BRCA1, BRCA2 or ATM qualifying mutations (Cohort A). Key Secondary Objectives: To determine the efficacy (as assessed by ORR) of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with BRCA1, BRCA2 or ATM qualifying gene mutations (Cohort A). To determine the efficacy (as assessed by rPFS) of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with HRR qualifying mutations (Cohort A+B). To determine the efficacy (as assessed by time to pain progression) of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with BRCA1, BRCA2 or ATM qualifying gene mutations (Cohort A). To determine the efficacy (as assessed by overall survival) of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with BRCA1, BRCA2 or ATM qualifying gene mutations (Cohort A). Other Secondary Objectives: To further assess the efficacy of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with BRCA1, BRCA2 or ATM qualifying gene mutations (Cohort A). To further assess the effect of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with BRCA1, BRCA2 or ATM qualifying gene mutations(Cohort A) on disease-related symptoms and health-related quality of life (HRQoL). To assess the efficacy of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with HRR qualifying gene mutations other than BRCA1, BRCA2 or ATM (Cohort B). To further assess the efficacy of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with HRR qualifying gene mutations (Cohort A+B). To further assess the effect of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with HRR qualifying gene mutations (Cohort A+B) on disease-related symptoms and health-related quality of life (HRQoL). To determine the exposure to olaparib in a subset of subjects receiving olaparib. Safety Objective: To evaluate the safety and tolerability of olaparib versus investigator choice of enzalutamide or abiraterone acetate.

Inclusion Criteria

  • Histologically confirmed diagnosis of prostate cancer.
  • Documented evidence of metastatic castration resistant prostate cancer (mCRPC).
  • Must have progressed on prior new hormonal agent (e.g., abiraterone acetate and/or enzalutamide) for the treatment of mCRPC.
  • Ongoing therapy with Luteinizing Hormone-Releasing Hormone (LHRH) analog or bilateral orchiectomy.
  • Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
  • Qualifying Homologous Recombination Repair (HRR) mutation in tumor tissue.

  • Exclusion Criteria

  • Any previous treatment with PARP inhibitor, including olaparib.
  • Potential participants who had any previous treatment with DNA-damaging cytotoxic chemotherapy (prior taxane chemotherapy allowed).
  • Other malignancy (including Myelodysplastic Syndrome (MDS) and Monoclonal Gammopathy of Undetermined Significance (MGUS)) within the last 5 years except: adequately treated non-melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥5 years.
  • Known brain metastases.