The purpose of this study is to determine how participants with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib versus treatment with physician's choice of abiraterone acetate, enzalutamide, or docetaxel.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
405
Rucaparib will be administered daily.
Abiraterone acetate and enzalutamide will be administered daily. Docetaxel will be administered every 3 weeks.
Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration
The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first). Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).
Time frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined
The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first). Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria (Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).
Time frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Mayo Clinic - Arizona
Phoenix, Arizona, United States
Arizona Oncology Associates - USOR
Tucson, Arizona, United States
University of Southern California
Beverly Hills, California, United States
Alliance Research Centers
Laguna Hills, California, United States
VA Greater Los Angeles Healthcare System
Los Angeles, California, United States
San Bernardino Urological Associates
San Bernardino, California, United States
Sharp Memorial Hospital
San Diego, California, United States
Pacific Hematology Oncology Associates
San Francisco, California, United States
San Francisco VA Health Care System
San Francisco, California, United States
...and 140 more locations
Overall Survival in Participants With a BRCA Alteration
Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participant was last known to be alive.
Time frame: From enrollment to completion of study (up to approximately 7 years)
Overall Survival in Participants With a BRCA or ATM Alteration Combined
Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participants was last known to be alive.
Time frame: From enrollment to completion of study (up to approximately 7 years)
Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration
ORR is defined as the percentage of participants with a confirmed best response of Complete response (CR) or Partial Response (PR) in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria is used to determine ORR (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment). CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Objective Response Rate (ORR) by IRR in Participants With a BRCA or ATM Alteration Combined
ORR is defined as the percentage of participants with a confirmed best response of Complete response (CR) or Partial Response (PR) in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria is used to determine ORR (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment). CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Duration of Response (DOR) by IRR in Participants With a BRCA Alteration
DOR is defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that Progressive Disease (PD) (using the same criteria) is documented.
Time frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Duration of Response (DOR) by IRR in Participants With a BRCA or ATM Alteration Combined
DOR is defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that Progressive Disease (PD) (using the same criteria) is documented.
Time frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
PSA Response in Participants With a BRCA Alteration
Confirmed PSA response is defined as ≥ 50% reduction in PSA from baseline on at least two assessments conducted at least 3 weeks apart. PSA response is calculated for all participants with PSA values at baseline and at least one post-baseline assessment. PSA is assessed by a local laboratory.
Time frame: From enrollment to primary completion of study (up to approximately 5 years)
PSA Response in Participants With a BRCA or ATM Alteration Combined
Confirmed PSA response is defined as ≥ 50% reduction in PSA from baseline on at least two assessments conducted at least 3 weeks apart. PSA response is calculated for all participants with PSA values at baseline and at least one post-baseline assessment. PSA is assessed by a local laboratory.
Time frame: From enrollment to primary completion of study (up to approximately 5 years)
Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration
Defined as the percentage of participants with a complete response (CR), partial response (PR), and stable disease (SD) according to modified RECIST Version 1.1 with no progression in bone per PCWG3 criteria.
Time frame: From enrollment to 6 months
Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined
Defined as the percentage of participants with a Complete Response (CR), Partial Response (PR), and Stable Disease (SD), according to Modified RECIST Version 1.1 with no progression in bone per PCWG3 Criteria.
Time frame: From enrollment to 6 months
Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration
Time to PSA progression is defined as the time from randomization to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline value for participants who did not have a decline in PSA) in PSA was measured. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.
Time frame: From enrollment to primary completion of study (up to approximately 5 years)
Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined
Time to PSA progression is defined as the time from randomization to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline value for participants who did not have a decline in PSA) in PSA was measured. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.
Time frame: From enrollment to primary completion of study (up to approximately 5 years)
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P
Changes in health and pain status from baseline to week 25 using: Functional Assessment of Cancer Therapy-Prostate questionnaire (FACT-P total score, on a scale of 0 to 156 where a higher score is better quality of life). The greater the decrease in score (ie more negative) from baseline to week 25 the greater the decrease in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) (during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.
Time frame: From enrollment to up to approximately 25 weeks
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF
Changes in health and pain status from baseline to week 25 using: Brief Pain Inventory-Short Form (BPI-SF) questionnaire (on a scale of 1 to 10, from mild to severe, for pain and pain-interference scores). A decrease indicates less severe pain/interference. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) (during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.
Time frame: From enrollment to up to approximately 25 weeks
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L
Changes in health and pain status from baseline to week 25 using: EuroQol-5D-5L Visual Analogue Scale (EQ-5D-5L VAS; on a scale from 100 to 0, from best to worst health status). The greater the increase in score (including more negative) from baseline to week 25 the greater the increase in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.
Time frame: From enrollment to up to approximately 25 weeks
Trough Plasma PK (Cmin) of Rucaparib Based on Sparse Sampling
Mean trough PK plasma concentration over time in the safety population with at least one PK sample collected at timepoints week 5, 9, 13 and 17; only Week 5 data presented.
Time frame: From enrollment to week 5 of dosing