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

URL:

https://clinicaltrials.gov/show/NCT02987543

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
abiraterone acetateZYTIGAEnzalutamide OR abiraterone acetate
enzalutamideXTANDIEnzalutamide 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 or tablets 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 or 500 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. Prednisolone is permitted for use instead of prednisone if necessary.
  • enzalutamide
  • abiraterone acetate
  • abiraterone acetate
  • enzalutamide

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 metastatic prostate cancer and/or CRPC .

          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,
             except if for non-prostate cancer indication and last dose > 5 years prior to
             randomization.

          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:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only
Time Frame:Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Safety Issue:
Description:The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a >=20% increase in the sum of diameters of target lesions and an absolute increase of >=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as >= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, >=6 weeks later, must show >=2 more new bone lesions (for a total of >=4 new bone lesions since baseline).

Secondary Outcome Measures

Measure:Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only
Time Frame:Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Safety Issue:
Description:ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = >=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR.
Measure:Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B
Time Frame:Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Safety Issue:
Description:The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.
Measure:Time to Pain Progression - Cohort A Only
Time Frame:Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Safety Issue:
Description:Time from randomisation to time point at which worsening in pain is observed (ie date of pain progression - date of randomisation + 1). Based on average Brief Pain Inventory - short form (BPI-SF) worst pain [Item 3] and Analgesic Quantification Algorithm [AQA] score.
Measure:Overall Survival (OS) - Cohort A Only
Time Frame:Approximately 35 months after the first patient was randomised.
Safety Issue:
Description:Number of Participants with Overall Survival (OS) - Cohort A only.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

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

Last Updated

August 4, 2021