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

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

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-000300-28-DK

Enrollment

340

Registered

2017-01-03

Start date

2017-05-16

Completion date

Unknown

Last updated

2019-06-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Metastatic castration-resistant prostate cancer MedDRA version: 20.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer

Interventions

Product Name: olaparib Product Code: AZD2281 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: olaparib CAS Number: 763113-22

Eligibility

Sex/Gender

Male

Inclusion criteria

Inclusion criteria: 1. Histologically confirmed diagnosis of prostate cancer. 2. Candidate for treatment with enzalutamide or abiraterone with documented evidence of 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 by the Lynparza HRR Assay Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 102 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 238

Exclusion criteria

Exclusion criteria: 1. Any previous treatment with PARP inhibitor, including olaparib 2. Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy. 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 myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML. 5. *Subjects with known brain metastases.

Design outcomes

Primary

Measure	Time frame
Main Objective: To determine the efficacy (as assessed by rPFS) of olaparib versus investigator choice of enzalutamide or abiraterone acetate in men with mCRPC with BRCA1, BRCA2 or ATM qualifying mutations (Cohort A) ; Secondary Objective: To determine the efficacy of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with HRR qualifying gene mutations measured by objective response rate in Cohort A, rPFS in Cohort A+B, time to pain progression in Cohort A and overall survival in Cohort A ;Primary end point(s): Radiological progression free survival (rPFS) by blinded independent central review (BICR) using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria; Timepoint(s) of evaluation of this end point: At baseline and every 8 weeks (± 7 days), relative to the date of randomization, until objective radiological disease progression by BICR using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria	—

Measure

Time frame

Main Objective: To determine the efficacy (as assessed by rPFS) of olaparib versus investigator choice of enzalutamide or abiraterone acetate in men with mCRPC with BRCA1, BRCA2 or ATM qualifying mutations (Cohort A) ; Secondary Objective: To determine the efficacy of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with HRR qualifying gene mutations measured by objective response rate in Cohort A, rPFS in Cohort A+B, time to pain progression in Cohort A and overall survival in Cohort A ;Primary end point(s): Radiological progression free survival (rPFS) by blinded independent central review (BICR) using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria; Timepoint(s) of evaluation of this end point: At baseline and every 8 weeks (± 7 days), relative to the date of randomization, until objective radiological disease progression by BICR using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria

—

Secondary

Measure	Time frame
Secondary end point(s): Confirmed ORR by BICR assessment in subjects with measurable disease using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria rPFS by BICR using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria Pain progression based on BPI-SF item 3 “worst pain in 24 hours” and opiate analgesic use (AQA score) Overall survival ; Timepoint(s) of evaluation of this end point: At baseline and every 8 weeks (± 7 days), relative to the date of randomization, until objective radiological disease progression by BICR Subjects will complete the BPI-SF daily on the ePRO device for the 7 days just prior to day 1 baseline visit and every 4 weeks The status of ongoing, withdrawn (from the study) and “lost to follow-up” subjects at the time of an overall survival analysis should be obtained by the site personnel by checking the subject notes, hospital records, contacting the subject’s general practitioner and checking publicly available death registries.	—

Measure

Time frame

Secondary end point(s): Confirmed ORR by BICR assessment in subjects with measurable disease using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria rPFS by BICR using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria Pain progression based on BPI-SF item 3 “worst pain in 24 hours” and opiate analgesic use (AQA score) Overall survival ; Timepoint(s) of evaluation of this end point: At baseline and every 8 weeks (± 7 days), relative to the date of randomization, until objective radiological disease progression by BICR Subjects will complete the BPI-SF daily on the ePRO device for the 7 days just prior to day 1 baseline visit and every 4 weeks The status of ongoing, withdrawn (from the study) and “lost to follow-up” subjects at the time of an overall survival analysis should be obtained by the site personnel by checking the subject notes, hospital records, contacting the subject’s general practitioner and checking publicly available death registries.

—

Countries

Argentina, Australia, Austria, Brazil, Canada, China, Denmark, France, Germany, Israel, Japan, Korea, Republic of, Netherlands, Norway, Spain, Sweden, Taiwan, United Kingdom, United States

Contacts

Public ContactClinical Trial Transparency

AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026