Combination Chemotherapy and Bevacizumab as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Biological: bevacizumab
- Registration Number
- NCT00719797
- Lead Sponsor
- Gruppo Oncologico del Nord-Ovest
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as irinotecan, oxaliplatin, leucovorin, and fluorouracil, 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. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.
PURPOSE: This randomized phase III trial is comparing two combination chemotherapy regimens given together with bevacizumab to see how well they work as first-line therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.
- Detailed Description
OBJECTIVES:
Primary
* To compare the progression-free survival of bevacizumab in combination with oxaliplatin, irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFOXIRI) versus bevacizumab in combination with irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI) in patients with unresectable, metastatic colorectal cancer.
Secondary
* To evaluate the safety profile, including long-term adverse events of these regimens in these patients.
* To compare the overall response rate, duration of response, and secondary R0 surgery rates of metastases and overall survival between treatment arms.
* To evaluate potential surrogate markers predictive of bevacizumab activity.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0 vs 1-2), prior adjuvant chemotherapy (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.
* Arm I (FOLFOXIRI): Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
* Arm II (FOLFIRI): Patients receive irinotecan hydrochloride IV over 1 hour, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
In both arms, treatment repeats every 2 weeks for up to 12 courses. Treatment with bevacizumab, fluorouracil, and leucovorin calcium continues in the absence of disease progression or unacceptable toxicity.
Patients undergo serum extraction and blood sample collection periodically for genotyping studies. Patients also undergo collection of tumoral sections from paraffin embedded primary and/or metastatic lesions periodically for immunohistochemical analyses.
After completion of study treatment, patients are followed every 8 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 509
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (FOLFOXIRI) bevacizumab Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Arm II (FOLFIRI) irinotecan hydrochloride Patients receive irinotecan hydrochloride IV over 1 hour, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Arm II (FOLFIRI) bevacizumab Patients receive irinotecan hydrochloride IV over 1 hour, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Arm II (FOLFIRI) leucovorin calcium Patients receive irinotecan hydrochloride IV over 1 hour, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Arm I (FOLFOXIRI) fluorouracil Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Arm I (FOLFOXIRI) irinotecan hydrochloride Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Arm I (FOLFOXIRI) leucovorin calcium Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Arm II (FOLFIRI) fluorouracil Patients receive irinotecan hydrochloride IV over 1 hour, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Arm I (FOLFOXIRI) oxaliplatin Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
- Primary Outcome Measures
Name Time Method Progression free survival up to 54 months To compare the progression free survival of bevacizumab in combination with oxaliplatin, irinotecan and infusional 5FU/LV ("GONO" FOLFOXIRI regimen) to bevacizumab in combination with irinotecan and infusional 5FU/LV (FOLFIRI regimen)
- Secondary Outcome Measures
Name Time Method Secondary R0 surgery rates of metastases up to 54 months Duration of response up to 54 months Overall survival up to 54 months Overall response rate up to 54 months Surrogate markers predictive of bevacizumab activity up to 54 months
Trial Locations
- Locations (44)
Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica
🇮🇹Alessandria, Italy
A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona - Ancona (An) Oncologia Medica
🇮🇹Ancona, Italy
P.O. Zona Aretina - Ospedale S. Donato Di Arezzo - Arezzo (Ar) Oncologia Medica
🇮🇹Arezzo, Italy
Irccs Centro Di Riferimento Oncologico (Cro) - Aviano (Pn) Oncologia Medica
🇮🇹Aviano, Italy
Ospedale S. Orsola F.B.F. - Brescia - Brescia (Bs) Oncologia Medica
🇮🇹Brescia, Italy
Istituto Ospedaliero Fondazione Poliambulanza Di Brescia - Brescia (Bs) Oncologia Medica
🇮🇹Brescia, Italy
Stabilimento "Perrino" - Brindisi - Brindisi (Br) Oncologia Medica
🇮🇹Brindisi, Italy
Azienda Ospedaliera S. Elia - Caltanissetta (Cl) Oncologia Medica
🇮🇹Caltanissetta, Italy
Ausl 1 Di Massa E Carrara - Carrara (Ms) Oncologia Medica
🇮🇹Carrara, Italy
Ospedale Cecina - Cecina (Li) Oncologia Medica
🇮🇹Cecina, Italy
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