This randomized, multi-center, active-controlled, open-label, parallel-group study will investigate the efficacy and safety of biomarker-driven maintenance treatment for first-line mCRC. Participants with mCRC are eligible for entry and cannot have received any prior chemotherapy in the metastatic setting. The entire study duration is anticipated to be approximately 7.5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,044
500 mg/m\^2 via IV infusion on Day 1 of every 2-week cycle
Administered per the Investigator's discretion in accordance with locally approved prescribing information.
Per Investigator's discretion: 5-FU 1600-2400 mg/m\^2 administered via 46-hour IV infusion on Day 1 of every 2-week cycle and LV 400 mg/m\^2 administered via a 2-hour infusion on Day 1 every 2 weeks or 1000 mg/m\^2 twice-daily capecitabine (BID) by mouth given days 1-14 every 2 weeks. The chosen fluoropyrimidine should be administered in accordance with local prescribing information.
Progression-Free Survival (PFS)
PFS is defined as the time from randomization to the first occurrence of disease progression according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
Time frame: From randomization until disease progression or death from any cause, up to 5 years
Overall Survival (OS)
OS is defined as the time from randomization into the MTP to time of death from any cause.
Time frame: From randomization until death from any cause, up to 5 years
Percentage of Participants With Adverse Events
Time frame: From baseline until end of study (up to 5 years)
Overall Response
Calculated as the number of participants with a best overall response of CR or PR according to RECIST 1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR= CR + PR.
Time frame: From randomization until disease progression, up to 5 years
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with CR, PR, or stable disease (SD) at 16 weeks. Per RECIST v1.1, CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
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800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle, or a fixed dose of 840 mg
960 mg vermurafenib BID by mouth
5 mg/kg bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle per local prescribing information
Initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses by IV infusion on Day 1 of every 3-week treatment cycle
Initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses by IV infusion on Day 1 of each 3-week treatment cycle
60 mg orally once daily for 3 weeks followed by a 1-week treatment break
1600-2400 mg/m\^2 5-FU via 46-hour IV infusion in combination with 400 mg/m\^2 LV via 2-hour infusion on Day 1 of every 2-week cycle until disease progression per the Investigator's assessment using modified Response Evaluation Criteria in Solid Tumors or death from any cause, whichever occurs first. The fluoropyrimidine should be administered in accordance with local prescribing information.
1000 mg/m\^2 twice-daily capecitabine (BID) by mouth given days 1-14 every 2 weeks. The fluoropyrimidine should be administered in accordance with local prescribing information.
Hospital de Gastroenterologia Dr. Bonorino Udaondo ; Servicio de Oncología
Buenos Aires, Argentina
Centro Oncologico Riojano Integral (CORI)
La Rioja, Argentina
Clínica Viedma
Viedma Rio Negro, Argentina
Institut Jules Bordet X
Brussels, Belgium
Hospital Erasme
Brussels, Belgium
UZ Leuven Gasthuisberg
Leuven, Belgium
CHC MontLégia
Liège, Belgium
AZ Delta (Campus Rumbeke)
Roeselare, Belgium
University Clinical Center of the Republic of Srpska
Banja Luka, Bosnia and Herzegovina
Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia
Passo Fundo, Rio Grande do Sul, Brazil
...and 144 more locations
Time frame: From randomization until disease progression, up to 5 years
Time to Treatment Response
Calculated as the time from randomization to the first Occurrence of a documented Objective Response (CR or PR) determined according to RECIST 1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: From randomization until disease progression or death from any cause, up to 5 years
Duration of Response
Defined as the time from the first assessment of CR or PR until disease progression or death from any cause, whichever occurs first. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: From first objective response until disease progression or death from any cause, up to 5 years
Percentage of Participants With Improvement and/or Stayed the Same on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
Time frame: From baseline until end of study (up to 5 years)