Clinical Trials /

Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)

NCT02987543

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)
  • Official 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)

Clinical Trial IDs

  • ORG STUDY ID: D081DC00007
  • NCT ID: NCT02987543

Conditions

  • Metastatic Castration-resistant Prostate Cancer

Interventions

DrugSynonymsArms
olaparibLynparzaOlaparib
enzalutamideXTANDIEnzalutamide OR abiraterone acetate
abiraterone acetateZYTIGAEnzalutamide OR abiraterone acetate

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
OlaparibExperimentalOlaparib 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
  • olaparib
Enzalutamide OR abiraterone acetateActive ComparatorEnzalutamide: 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.
  • enzalutamide
  • abiraterone acetate

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in radiographic progression free survival (rPFS)
Time Frame:During study period (up to 3 years)
Safety Issue:
Description:rPFS in subjects with BRCA1, BRCA2, or ATM qualifying gene mutations defined as the time from randomization to radiographic progression by blinded independent central reader (BICR) using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria or death.

Secondary Outcome Measures

Measure:Confirmed Objective Response Rate (ORR) by BICR
Time Frame:During study period (up to 3 years)
Safety Issue:
Description:Confirmed ORR by BICR in subjects with measurable disease using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria
Measure:Time to Pain progression
Time Frame:To be completed by subject daily for 7 consecutive days before each respective 4-week visit/assessment date with Day 1 as the baseline visit date (not required to be at site)
Safety Issue:
Description:Time to pain progression defined as the time from randomization to increase in pain based on brief pain inventory (short form) question #3 and opioid analgesic usage
Measure:Overall Survival (OS)
Time Frame:During study period (up to 4 years)
Safety Issue:
Description:OS defined as time from randomization to death due to any cause
Measure:rPFS
Time Frame:During study period (up to 3 years)
Safety Issue:
Description:rPFS in subjects with HRR qualifying mutations defined as the time from randomization to radiographic progression by blinded independent central reader (BICR) using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria or death
Measure:AEs/SAEs and Collection of clinical chemistry/hematology parameters
Time Frame:From the time of signature of informed consent throughout the treatment period up to and including the 30-day follow-up period.
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • metastatic castration-resistant prostate cancer (mCRPC)
  • homologous recombination repair (HRR)

Last Updated

February 14, 2018