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

This study is currently recruiting participants.
Verified November 2017 by AstraZeneca
Sponsor:
ClinicalTrials.gov Identifier:
NCT02987543
First Posted: December 9, 2016
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
AstraZeneca
  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 Intervention Phase
Metastatic Castration-resistant Prostate Cancer Drug: olaparib Drug: enzalutamide Drug: abiraterone acetate Phase 3

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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Change in radiographic progression free survival (rPFS) [ Time Frame: During study period (up to 3 years) ]
    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:
  • Confirmed Objective Response Rate (ORR) by BICR [ Time Frame: During study period (up to 3 years) ]
    Confirmed ORR by BICR in subjects with measurable disease using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria

  • 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) ]
    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

  • Overall Survival (OS) [ Time Frame: During study period (up to 4 years) ]
    OS defined as time from randomization to death due to any cause

  • rPFS [ Time Frame: During study period (up to 3 years) ]
    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

  • 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. ]

Estimated Enrollment: 340
Actual Study Start Date: February 6, 2017
Estimated Study Completion Date: February 5, 2021
Estimated Primary Completion Date: March 20, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: XTANDI
Drug: abiraterone acetate
1,000 mg (4 x 250 mg tablets) once daily
Other Name: ZYTIGA

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02987543


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

  Show 242 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Johann de Bono, M.D., Ph.D. The Institute of Cancer Research, United Kingdom
Principal Investigator: Maha Hussain, M.D., FACP, FASCO Northwestern University, United States of America
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02987543     History of Changes
Other Study ID Numbers: D081DC00007
First Submitted: November 15, 2016
First Posted: December 9, 2016
Last Update Posted: November 17, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
metastatic castration-resistant prostate cancer (mCRPC)
homologous recombination repair (HRR)

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Olaparib
Abiraterone Acetate
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 Enzyme Inhibitors