The purpose of this study is to assess the efficacy of FOLFOX + panitumumab followed by FOLFIRI + bevacizumab (Sequence 1) versus FOLFOX + bevacizumab followed by FOLFIRI + panitumumab (Sequence 2) in untreated patients with wild-type RAS metastatic, primary left-sided, unresectable colorectal cancer
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
419
oxaliplatin 85 mg/m2 administered by IV infusion over 120 minutes on Day 1, L-leucovorin 200 mg/m2 administered as a 2-hour IV infusion on Day 1 and 5-FU 400 mg/m2 administered as IV bolus over approximately 2 to 4 minutes on Day 1 followed by 5-FU 2400 mg/m2 administered as IV infusion over 46- 48 hours on Days 1 and 2
6 mg/kg administered by intravenous (IV) infusion over 60 minutes on Day 1 of each 14-day cycle
5 mg/kg administered by IV infusion over 60 minutes on Day 1 of each 14-day cycle
irinotecan 180 mg/m2 administered as a 90 minutes IV infusion on Day 1, L-leucovorin 200 mg/m2 administered as a 2-hour IV infusion on Day 1 and 5-FU 400 mg/m2 administered as IV bolus over approximately 2 to 4 minutes on Day 1 followed by 5-FU 2400 mg/m2 administered as IV infusion over 46-48 hours on Days 1 and 2
Spanish Cooperative Group for the Treatment of Digestive Tumors
Madrid, Spain
Progression-free survival rate at 35 months
35-month PFSR defined as the number of patients, who at 35 months after randomization, have not had second or first disease progression nor died (due to any cause), over the total number of evaluable patients.
Time frame: 35 months after date of randomization
overall survival rate at 35 months
35-month OSR defined as the number of patients who at 35 months after randomization have not died over the total number of evaluable patients.
Time frame: 35 months after date of randomization
overall survival
OS defined as the time from randomization to the date of death (due to any cause), with patients alive or lost to follow-up at the analysis data cut-off date censored at their last contact date.
Time frame: Baseline through the end of the study (up 72 months)
progression-free from randomization to second progression or death
Total PFS defined as the time from randomization to second disease progression (i.e. progression during the second-line treatment) or death (due to any cause).
Time frame: Baseline through the end of the study (up 72 months)
progression-free survival in first-line treatment and in second-line treatment
PFS in first-line treatment defined as the time from randomization to disease progression or death (due to any cause) during first-line treatment. PFS in second-line treatment defined as the time from the date of second-line treatment initiation to disease progression or death (due to any cause) during secondline treatment.
Time frame: Baseline through the end of the study (up 72 months)
time to first-line treatment failure and to second-line treatment failure
Time to first-line treatment failure defined as the time form randomization to disease progression, death (due to any cause) or discontinuation due to toxicity during first-line treatment. Time to second-line treatment failure defined as the time from the date of second-line treatment initiation to disease progression, death (due to any cause) or discontinuation due to toxicity during second-line treatment.
Time frame: 72 months
objective response rate
Proportion of patients with an objective response (complete or partial response) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria in first-line treatment and in second-line treatment.
Time frame: Baseline through the end of the study (up 72 months)
proportion of patients with Early Tumour Shrinkage
Proportion of patients with ETS in first-line treatment and in second-line treatment. ETS will be defined as a reduction in tumour size ≥30% (RECIST 1.1 criteria) at the first evaluation (i.e. week 12)
Time frame: Baseline through the end of the study (up 72 months)
Depth of Response
DpR measured as the maximum decrease in target measurement (RECIST 1.1 criteria) during the complete course of evaluation in first-line treatment and in second-line treatment.
Time frame: Baseline through the end of the study (up 72 months)
disease control rate
Proportion of patients with disease control (complete, partial response or stable disease) in first-line treatment and in second-line treatment.
Time frame: Baseline through the end of the study (up 72 months)
duration of disease control
Duration of disease control defined as time from first confirmed disease control to disease progression per RECIST 1.1 criteria or death (due to any cause) in first-line treatment and in second-line treatment. For patients with disease control who have not progressed or died at last observation, duration of disease control will be censored at their last evaluable disease assessment date.
Time frame: Baseline through the end of the study (up 72 months)
duration of response
Duration of response defined as time from first confirmed objective response to disease progression per RECIST 1.1 criteria or death (due to any cause) in first-line treatment and in second-line treatment. For patients with response who have not progressed or died at last observation, duration of response will be censored at their last evaluable disease assessment date.
Time frame: Baseline through the end of the study (up 72 months)
time to response
Time to response in first-line treatment defined as the time from randomization to the date of first confirmed objective response per RECIST 1.1 criteria during first-line treatment. Time to response in second-line treatment defined as the time from the date of second-line treatment initiation to the date of first confirmed objective response per RECIST 1.1 criteria during second-line treatment.
Time frame: Baseline through the end of the study (up 72 months)
Incidence and severity of AEs CTCAE v4.03 criteria
Safety assessment will consist of monitoring adverse events (AEs), including AEs of special interest, serious AEs (SAEs) and laboratory safety parameters. AEs will be graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03.
Time frame: Baseline through the end of the study (up 72 months)
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