Multicenter Phase III Randomized Study of FOLFIRI Plus Bevacizumab Following or Not by a Maintenance Therapy With Bevacizumab in Patients With Non-Pretreated Metastatic Colorectal Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
Multicenter Phase III Randomized Study of FOLFIRI Plus Bevacizumab Following or Not by a Maintenance Therapy With Bevacizumab in Patients With Non-Pretreated Metastatic Colorectal Cancer
OBJECTIVES:
Primary
- Compare disease-control duration in patients with metastatic colorectal cancer
receiving FOLFIRI chemotherapy in combination with bevacizumab with or without
bevacizumab maintenance therapy.
Secondary
- Determine objective response rate.
- Determine non-hematologic grade 3-4 (except alopecia) toxicity rate.
- Determine overall toxicity rate.
- Determine duration of chemotherapy-free interval.
- Determine progression-free survival.
- Determine overall survival.
- Determine time-to-treatment failure.
- Determine quality of life (EORTC QLQ-C30).
- Complete geriatric evaluation.
OUTLINE: This is a multicenter study. Patients are stratified according to cancer center,
primary tumor (resected vs unresected), and Köhne criteria (low vs intermediate vs high).
Patients are randomized to 1 of 2 treatment arms.
- Arm A: Patients receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV
over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV
over 46 hours on days 1-2. Chemotherapy treatment repeats every 2 weeks for 12 courses.
Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks during
chemotherapy. Patients then receive bevacizumab maintenance therapy once every 2 weeks
during the chemotherapy-free interval.
- Arm B: Patients receive FOLFIRI chemotherapy and bevacizumab as in arm A. Patients
receive no treatment during the chemotherapy-free interval.
In all arms, the chemotherapy treatment and the chemotherapy-free interval treatment repeats
in the absence of disease progression during the chemotherapy portion or unacceptable
toxicity. Patients who progress during the chemotherapy-free interval will receive 12 more
courses of chemotherapy.
All patients complete quality of life questionnaires (QLQ-30) and patients ≥ 75 also
complete the geriatric questionnaire at baseline and every 8 weeks during study treatment.
After completion of study treatment, patients are followed up every 8 weeks.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed colorectal cancer
- Metastatic disease
- Not a candidate for curative surgery
- At least 1 tumor target measurable by RECIST criteria
- No metastasis potentially resectable after receiving chemotherapy
- No occlusive tumors
- No macronodular peritoneal carcinomatosis
- No known or suspected CNS metastases
PATIENT CHARACTERISTICS:
- OMS status 0-2
- Life expectancy ≥ 3 months
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN in the presence of hepatic
metastases)
- Creatinine ≤ 1.5 times ULN
- Proteinuria ≤1 g
- Not pregnant or nursing
- No gastroduodenal ulcer, wound, or fractured bone
- No acute or subacute intestinal occlusion or history of inflammatory bowel disease or
large resection of small bowel
- No clinically relevant coronary artery disease or a history of a myocardial
infarction within the last 6 months
- No uncontrolled hypertension while receiving chronic medication
- No other malignancy within the past 5 years except for basal cell carcinoma of the
skin or pre-invasive carcinoma of the cervix
- No medical or psychological condition which, in the opinion of the investigator,
would not permit the patient to complete the study
PRIOR CONCURRENT THERAPY:
- See Patient Characteristics
- No prior chemotherapy for metastatic disease
- Adjuvant chemotherapy allowed provided it was completed > 6 months ago
- No prior irinotecan or other antiangiogenic therapy
- At least 4 weeks since surgery (except for diagnostic biopsy) or irradiation
- No other drugs not allowed for medical reasons
- Concurrent oral anticoagulants (e.g., coumadin, warfarin) allowed provided the INR is
closely monitored
- A change of anticoagulants to low-molecular weight heparin is preferred
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Disease-control duration
Outcome Time Frame:
one year after last patient included
Safety Issue:
No
Principal Investigator
Thomas Aparicio
Investigator Role:
Principal Investigator
Investigator Affiliation:
Hopital Avicenne BOBIGNY
Authority:
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Study ID:
CDR0000636983
NCT ID:
NCT00952029
Start Date:
March 2010
Completion Date:
July 2015
Related Keywords:
- Colorectal Cancer
- stage IV colon cancer
- stage IV rectal cancer
- Colorectal Neoplasms
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