Purpose

The purpose of this study is to evaluate the efficacy and safety of olaparib versus enzalutamide or abiraterone acetate in subjects with metastatic castration-resistant prostate cancer who have failed prior treatment with a new hormonal agent and have homologous recombination repair gene mutations.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Histologically confirmed diagnosis of prostate cancer.
  2. Documented evidence of metastatic castration resistant prostate cancer (mCRPC).
  3. Subjects must have progressed on prior new hormonal agent (e.g. abiraterone acetate and/or enzalutamide) for the treatment of mCRPC.
  4. Ongoing therapy with LHRH analog or bilateral orchiectomy.
  5. Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
  6. Qualifying HRR mutation in tumor tissue.

Exclusion Criteria

  1. Any previous treatment with PARP inhibitor, including olaparib.
  2. Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy (prior taxane chemotherapy allowed).
  3. Other malignancy (including MDS and 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.
  4. Subjects with known brain metastases.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Olaparib
Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose of 300 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions
  • Drug: olaparib
    300 mg (2x 150 mg tablets) twice daily
    Other names:
    • Lynparza
Active Comparator
Enzalutamide OR abiraterone acetate
Enzalutamide: Enzalutamide is available as capsules containing 40 mg of enzalutamide. Subjects will be administered study treatment orally at a dose of 160 mg once daily. Abiraterone acetate with prednisone: Abiraterone acetate is available as tablets containing 250 mg of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily in combination with prednisone 5 mg administered twice daily orally.
  • Drug: enzalutamide
    160 mg (4 x 40 mg capsules) once daily
    Other names:
    • XTANDI
  • Drug: abiraterone acetate
    1,000 mg (4 x 250 mg tablets) once daily
    Other names:
    • ZYTIGA

Recruiting Locations

Research Site
Nashville, Tennessee 37232

More Details

NCT ID
NCT02987543
Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

Detailed Description

This is a prospective, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of olaparib versus enzalutamide or abiraterone in subjects with metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with a new hormonal agent (NHA) and have a qualifying tumor mutation in one of 15 genes involved in the homologous recombination repair (HRR) pathway. Subjects will be divided into two cohorts based on HRR gene mutation status.

Approximately 340 subjects will be randomized 2:1 (olaparib : investigator choice of enzalutamide or abiraterone acetate) into the trial.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.