RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab (Bv) may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving combination chemotherapy together with bevacizumab is more effective than combination chemotherapy alone in treating colon cancer in adjuvant setting. PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens with or without bevacizumab to compare how well they work in treating patients who have undergone surgery for high risk stage II or stage III colon cancer.
This was an open-label Phase III, multicenter, multinational, randomized, 3-arm study designed to evaluate the efficacy and safety of bevacizumab in combination with either intermittent fluorouracil/leucovorin with oxaliplatin (FOLFOX4) or capecitabine plus oxaliplatin (XELOX) versus FOLFOX4 regimen alone, as adjuvant chemotherapy in colon carcinoma. The treatment phase consisted of two parts of 24 weeks for a total of 48 weeks. The first part (weeks 1 to 24) consisted of treatment with either FOLFOX4, FOLFOX4 in combination with bevacizumab, or XELOX in combination with bevacizumab. The second part (weeks 25 to 48) consisted of single-agent bevacizumab for patients randomized to either bevacizumab-containing arm, but was only an observation period for patients assigned to the FOLFOX4-alone arm. Patients were to be followed for recurrence/new occurrence of colorectal cancer and survival. Patients who experienced a confirmed recurrence, occurrence of a new colorectal cancer during therapy, or experienced unacceptable toxicity were to be taken off study treatment but remain in study follow-up. Patients that came off therapy due to a confirmed recurrence/appearance of new colorectal cancer, were to be followed for survival until the end of the study follow-up period. The primary analysis was performed 36 months after the last patient has been randomized. After the primary analysis, patients continue to be followed for survival for at least a further 2 years ie, until all patients have been followed-up for at least 5 years following randomization.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
3,451
Administered as an intravenous infusion over 30 - 90 minutes.
Film-coated tablets
Administered as either a bolus injection or continuous intravenous infusion over 22 hours.
Administered as a 200 mg/m\^2 infusion over 2 hours.
Administered as an intravenous infusion over 2 hours.
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States
Disease-free Survival in Stage III Cancer Patients - Time to Event
Disease-free survival (DFS) was defined as the time from the date of randomization to the time of a recurrence, a new occurrence of colorectal cancer or death due to any cause, whichever occurred first. Patients without an event were censored at the last date the patient was known to be disease-free. Recurrence and new occurrence of colorectal cancer were based on tumor assessments made by the investigator. Patients with no tumor assessments after baseline but still alive at the time of the clinical cut-off were censored at day 1.
Time frame: From first patient randomized until the data cut-off date of 30 June 2010 (36 months after the last patient randomized).
Disease-free Survival in Stage III Cancer Patients - Number of Events
A disease-free survival (DFS) event was composed of a recurrence, a new occurrence of colorectal cancer or death due to any cause. Recurrence and new occurrence of colorectal cancer were based on tumor assessments made by the investigator. Triggering events for DFS are reported; a patient can have both recurrence and a new occurrence of colon cancer.
Time frame: From first patient randomized until the data cut-off date of 30 June 2010 (36 months after the last patient randomized).
Overall Survival in Stage III Cancer Patients - Time to Event
Overall survival was defined as the time between date of randomization and date of death due to any cause. Patients not reported as having died at the time of the analysis were censored at the date they were last known to be alive.
Time frame: From first patient randomized until the clinical data cut-off date of 30 June 2010 (36 months after the last patient randomized).
Overall Survival in Stage III Cancer Patients - Number of Events
An overall survival event was death due to any cause.
Time frame: From first patient randomized until the clinical data cut-off date of 30 June 2010 (36 months after the last patient randomized).
Overall Survival in Stage III Cancer Patients - Time to Event: Final Analysis
Overall survival was defined as the time between date of randomization and date of death due to any cause. Patients not reported as having died at the time of the clinical cut-off date (30 June 2012) were censored at the date they were last known to be alive.
Time frame: From first patient randomized until the final data cut-off date of 30 June 2012 (5 years after the last patient randomized).
Overall Survival in Stage III Cancer Patients - Number of Events: Final Analysis
An overall survival event was death due to any cause.
Time frame: From first patient randomized until the final data cut-off date of 30 June 2012 (5 years after the last patient randomized).
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