This is an efficacy and safety study of olaparib alone or in combination with bevacizumab being compared to bevacizumab with a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer who have not progressed following first-line induction. The primary hypotheses are: Olaparib + Bevacizumab is superior to a fluoropyrimidine + Bevacizumab with respect to progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR); Olaparib is superior to a fluoropyrimidine + Bevacizumab with respect to PFS using RECIST 1.1 as assessed by BICR. As of amendment 5 study enrollment is being discontinued and study participants randomized to one of the two experimental arms (olaparib plus bevacizumab or olaparib monotherapy) must discontinue study intervention. Participants who are still on study treatment will no longer have tumor response assessments by BICR.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
335
300 mg BID, oral until progressive disease or end of study
2400 mg/m\^2 over 46 to 48 hours Q2W IV infusion until disease progression or end of study; bolus 5-FU (400mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion
5 mg/kg or 7.5 mg/kg Q2W or Q3W IV infusion until progressive disease or end of study
1000 mg/m\^2 oral capsule BID for 14 days, then 7 days off, Q3W) until progressive disease or end of study
400 mg/m\^2 (leucovorin) or 200 mg/m\^2 (levoleucovorin) may be added to Bevacizumab + 5-FU per investigator's discretion Q2W IV infusion until progressive disease or end of study
Providence Saint Joseph Medical Center, Disney Family Cancer ( Site 1392)
Burbank, California, United States
St Joseph Heritage Healthcare-Oncology ( Site 1383)
Fullerton, California, United States
UC Health Memorial Hospital ( Site 1401)
Colorado Springs, Colorado, United States
Poudre Valley Health System ( Site 1402)
Fort Collins, Colorado, United States
University Cancer & Blood Center, LLC ( Site 1381)
Athens, Georgia, United States
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS using RECIST 1.1 as assessed by BICR is presented.
Time frame: Up to approximately 30 months
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. The OS is presented.
Time frame: Up to approximately 30 months
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Time frame: Up to approximately 30 months
Number of Participants With One or More Adverse Events (AE)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced at least one AE was reported for each arm.
Time frame: Up to approximately 30 months
Number of Participants Discontinuing Study Intervention Due to an AE
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study intervention due to an AE was reported for each arm.
Time frame: Up to approximately 30 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. DOR is defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis will be censored at the date of their last tumor assessment. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions is also considered PD. DOR assessments will be based on BICR with confirmation. The DOR as assessed using RECIST 1.1 for all participants who experience a confirmed CR or PR will be presented.
Time frame: Up to approximately 30 months
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University of Chicago ( Site 1357)
Chicago, Illinois, United States
Illinois Cancer Care, PC ( Site 1352)
Peoria, Illinois, United States
James Graham Brown Cancer Center ( Site 1393)
Louisville, Kentucky, United States
University Medical Center New Orleans ( Site 1365)
New Orleans, Louisiana, United States
New England Cancer Specialists ( Site 1422)
Scarborough, Maine, United States
...and 119 more locations