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Completed

NCT Number: NCT02987543

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

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.

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Key information

Conditions

Metastatic Castration-resistant Prostate Cancer

Age range

18 year–130 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically confirmed diagnosis of prostate cancer.
  • Documented evidence of metastatic castration resistant prostate cancer (mCRPC).
  • 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 .
  • Ongoing therapy with LHRH analog or bilateral orchiectomy.
  • Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
  • Qualifying HRR mutation in tumor tissue.

Exclusion criteria

  • Any previous treatment with PARP inhibitor, including olaparib.
  • 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.
  • 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.
  • Subjects with known brain metastases.

Treatment and study plan

Olaparib

Drug

300 mg (2x 150 mg tablets) twice daily

Other names: Lynparza

Enzalutamide

Drug

160 mg (4 x 40 mg capsules) once daily

Other names: XTANDI

Abiraterone Acetate

Drug

1,000 mg (4 x 250 mg tablets) once daily

Other names: ZYTIGA

Primary outcomes

  1. 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).

    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 outcomes

  1. 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).

    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.

  2. 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).

    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.

  3. 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).

    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.

  4. Overall Survival (OS) - Cohort A Only

    Time frame: Approximately 35 months after the first patient was randomised.

    Number of Participants with Overall Survival (OS) - Cohort A only.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Foundation Medicine
  • Merck Sharp & Dohme LLC
  • Myriad Genetics, Inc.

Registry information

Official 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)

Important dates

Study start
2017
Primary completion
2019
Study completion
2023
First posted
Dec 9, 2016
Registry last updated
Oct 6, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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