A Randomized, Open-label Study to Assess the Efficacy and Safety of Olaparib Versus Enzalutamide or Abiraterone Acetate in Chinese Men With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have BRCA1/2 Mutations (PROfound-CN)
Trial Snapshot
- Phase
- Phase 4
- Status
- Active, not recruiting
- Sponsor
- AstraZeneca
- Enrollment
- 43
- Locations
- 36
- Primary Endpoint
- Radiological Progression-free Survival - Based on Blinded Independent Central Review (BICR)
Study Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of Olaparib compared with standard of care (Enzalutamide or Abiraterone Acetate) in Chinese men with metastatic castration-resistant prostate cancer who have failed prior treatment with a new hormonal agent and have BRCA1/2 mutations.
Detailed Description
This is a Phase IV, randomized, open-label, 2-arm, multicenter study evaluating the efficacy and safety of olaparib in Chinese men with metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with a new hormonal agent (NHA) and have BRCA1/2 mutations. Approximately 42 subjects will be randomized in a 2:1 ratio to olaparib or to investigator's choice of NHA (enzalutamide or abiraterone acetate).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
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.
- •Radiological progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
- •Deleterious or suspected deleterious BRCA1/2 mutation in tumor tissue.
- •Normal organ and bone marrow function measured within 28 days prior to administration of study treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
Exclusion Criteria
- •Any previous treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor, including olaparib.
- •Subjects who had any previous treatment with DNA-damaging cytotoxic chemotherapy, except if for non-prostate cancer indication and last dose > 5 years prior to randomization.
- •History of another primary malignancy except for malignancy treated with curative intent with no known active disease for ≥5 years before the first dose of study intervention and of low potential risk for recurrence.
- •Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
Arms & Interventions
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
Intervention: olaparib (Drug)
Enzalutamide OR abiraterone acetate
Enzalutamide:
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 of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily. Prednisone is 5mg twice daily. Prednisolone is permitted for use instead of prednisone if necessary.
Intervention: enzalutamide (Drug)
Enzalutamide OR abiraterone acetate
Enzalutamide:
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 of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily. Prednisone is 5mg twice daily. Prednisolone is permitted for use instead of prednisone if necessary.
Intervention: abiraterone acetate (Drug)
Enzalutamide OR abiraterone acetate
Enzalutamide:
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 of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily. Prednisone is 5mg twice daily. Prednisolone is permitted for use instead of prednisone if necessary.
Intervention: Prednisone (Drug)
Outcomes
Primary Outcomes
Radiological Progression-free Survival - Based on Blinded Independent Central Review (BICR)
Time Frame: Tumor assessments every 8 weeks (± 1 week) relative to the date of randomization until radiological progression as assessed by BICR or death (median duration of treatment of 9 and 6 months for Olaparib and Investigators Choice of NHA respectively).
rPFS is defined as the time from randomization until the date of objective disease progression (soft tissue or bone) or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression.
Secondary Outcomes
- Confirmed Objective Response Rate (ORR), Based on Blinded Independent Review (BICR)(Tumor assessments every 8 weeks (± 1 week) from randomisation until radiographic progression assessed by BICR (median duration of treatment of 9 and 6 months for Olaparib and Investigators Choice of NHA respectively).)
- Overall Survival(From the time from the date of randomization until death due to any cause. Assessments continue up to 27 months after the first patient was randomized.)
- Time to First Symptomatic Skeletal-related Event(Time from randomization to the first SSRE-radiation for skeletal symptoms, confirmed pathological fracture, confirmed spinal cord compression, or orthopaedic surgery for bone metastases. Assessments continue up to 27 months post first patient enrolled.)
- Time to Opiate Use for Cancer-related Pain(Opioid use will be recorded at baseline and at every study visit, including the safety follow-up visit. Assessments continue up to 27 months post first patient enrolled.)
- Prostate-specific Antigen Response(Blood samples for PSA assessment will be collected at baseline and every 4 weeks throughout the treatment phase, including at the study treatment discontinuation visit. Assessments continue up to 27 months post first patient enrolled.)
- Time From Randomization to Second Progression or Death(Tumor assessments will be performed every 8 weeks (±7 days) after randomization until radiologic progression or death, unless the participant withdraws consent. Assessments continue up to 27 months post first patient enrolled.)
- Subsequent Anticancer Therapy(Recorded from post discontinuation of study treatment up to primary data cut off date. Assessments continue up to 27 months post first patient enrolled.)