The purpose of this study is to evaluate the efficacy and safety (including evaluating side effects) of combination of olaparib and abiraterone versus placebo and abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) who have received no prior cytotoxic chemotherapy or new hormonal agents (NHAs) at metastatic castration-resistant prostate cancer (mCRPC) stage.
PROpel is a phase III study evaluating the efficacy, safety, and tolerability of olaparib versus placebo when given in addition to abiraterone to patients with metastatic castration-resistant prostate cancer (mCRPC) who have not received prior chemotherapy or new hormonal agents (NHAs) for metastatic castration-resistant prostate cancer (mCRPC) (first-line setting). Approximately 720 patients globally were planned to be randomized in PROpel in a 1:1 ratio to treatment with either olaparib and abiraterone or placebo and abiraterone. Enrolment had completed with a total of 796 patients randomised. Following the completion of global enrolment, the China cohort will randomise approximately 108 additional patients at sites in China, also in a 1:1 ratio. Patients will receive oral treatment with olaparib 300 mg twice daily + abiraterone 1000 mg once daily or placebo twice daily + abiraterone 1000 mg once daily. Patients in both treatment groups will also receive either prednisone or prednisolone 5 mg twice daily.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
895
300 mg (2 x 150 milligrams (mg) tablets) twice daily
1000 milligrams (mg) once daily
Number of Participants With Radiological Progression Free Survival (rPFS) Event by Investigator Assessment
An rPFS event is defined as progression determined by Response Evaluation Criteria in Solid Tumours version 1.1 \[RECIST 1.1\] and/or Prostate Cancer Working Group 3 \[PCWG-3\] or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomised therapy or receives another anticancer therapy prior to progression. Per RECIST v1.1, progression is defined as the sum of TLs has a 20% and absolute ≥ 5mm increase from nadir, and/or unequivocal progression in any non target lesions, and/or any new lesion identified. Per PCWG3, progression on a bone scan is defined as 2 or more new lesions observed from the first visit after baseline compared to baseline, or from all other visits compared to first visit after baseline. A confirmatory scan is required.
Time frame: Assessed from date of randomisation to data cut off (DCO1): 30Jul2021 (Approx. 2 years 9 months)
Number of Participants With Overall Survival (OS) Event
An OS event is defined as death by any cause, regardless of whether the patient withdraws from randomised therapy or receives another anticancer therapy.
Time frame: Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months). DCO3 is the final data cut-off for the OS analysis and therefore no further updates will be made.
Number of Participants With Time to First Subsequent Anticancer Therapy or Death (TFST) Event
A TFST (excluding radiotherapy) event is defined as the start of the first subsequent anticancer therapy after discontinuation of randomised treatment or death from any cause.
Time frame: Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Number of Participants With Time to Pain Progression (TTPP) Event
A TTPP event is defined as pain progression based on the Brief Pain Inventory-Short Form (BPI-SF) Item 3 (range 0-10, a higher score indicates worse pain) and opiate analgesic use (Analgesic quantification algorithm \[AQA\] score, range 0-7, a higher score indicates increased opioid use). For patients who are asymptomatic at baseline (average worst pain score of 0 and not taking opioids): A ≥2 point change from baseline in average (4-7 days) worst pain score observed at 2 consecutive visits or initiation of opioid use; For patients who are symptomatic at baseline (average worst pain score \>0 and/or receiving opioids): A ≥2 point change from baseline in average (4-7 days) worst pain score observed at 2 consecutive visits and an average worst pain score ≥4, and no decrease in average opioid use (≥1-point decrease in AQA score from a starting value of ≥2), or increase in opioid use (≥1-point increase, or ≥2-point increase if the starting value is 0) at 2 consecutive follow-up visits.
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Research Site
Birmingham, Alabama, United States
Research Site
Anchorage, Alaska, United States
Research Site
Tucson, Arizona, United States
Research Site
Tucson, Arizona, United States
Research Site
Clovis, California, United States
Research Site
Los Angeles, California, United States
Research Site
Los Angeles, California, United States
Research Site
Sacramento, California, United States
Research Site
San Diego, California, United States
Research Site
Denver, Colorado, United States
...and 122 more locations
Time frame: Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Number of Participants With Opiate Use
An event for opiate use is defined as the first opiate use for cancer related pain.
Time frame: Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Number of Participants With First Symptomatic Skeletal Related Event (SSRE)
An SSRE event is defined as the first sympomatic skeletal-related event defined by * Use of radiation therapy to prevent or relieve skeletal symptoms. * Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral).
Time frame: Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Number of Participants With Second Progression or Death (PFS2) Event
An event for PFS2 is defined as the second progression on next-line anticancer therapy or death, whichever occurs earlier.
Time frame: Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Brief Pain Inventory-Short Form (BPI-SF)
The BPI-SF is a validated, 15-item domain-specific instrument designed to assess the severity of pain and the impact/interference of pain on daily functions. BPI-SF worst pain, pain severity and pain interference score changes can be a minimum of -10 and a maximum of 10. A negative change from baseline value indicates improvement.
Time frame: Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Functional Assessment of Cancer Therapy- Prostate Cancer (FACT-P)
Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) total score and Functional Assessment of Cancer Therapy-General (FACT-G) total score. Total FACT-P score is the sum of Physical Well-being (PWB), Social Well-being (SWB), Emotional Well-being (EWB), Functional Well-being (FWB) and Prostate cancer subscale (PCS). FACT-P total score change from baseline values can be a minimum of -156 and a maximum of 156. A positive value indicates improvement. FACT-G total score is the sum of PWB, SWB, EWB and FWB. FACT-G Total score change from baseline values can be a minimum of -108 and a maximum of 108. A positive value indicates improvement.
Time frame: Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)