Second-Line Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer Who Have Received First-Line Chemotherapy and Bevacizumab
- Conditions
- Colorectal Cancer
- Interventions
- Biological: bevacizumab
- Registration Number
- NCT00720512
- 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. It is not yet known whether combination chemotherapy is more effective with or without bevacizumab in treating metastatic colorectal cancer.
PURPOSE: This randomized phase III trial is studying second-line combination chemotherapy to see how well it works compared with or without bevacizumab in treating patients with metastatic colorectal cancer who have received first-line chemotherapy and bevacizumab.
- Detailed Description
OBJECTIVES:
Primary
* To compare the progression-free survival of second-line chemotherapy with or without bevacizumab in patients with metastatic colorectal cancer who have received first-line chemotherapy with bevacizumab.
Secondary
* To compare the overall survival, response rate, and safety profile of second-line chemotherapy of these regimens in these patients.
* To conduct pharmacogenomics assessment of candidate variants in the VEGF gene and evaluate their association with progression-free survival and other study outcomes.
OUTLINE: This is a multicenter study. Patients are stratified according to participating center, ECOG performance status (0 vs 1-2), disease-free interval from the last administration of first-line chemotherapy for metastatic disease (≤ 3 months vs \> 3 months), and type of second-line chemotherapy (irinotecan hydrochloride, leucovorin calcium, and fluorouracil \[FOLFIRI\] vs oxaliplatin, leucovorin calcium, and fluorouracil \[mFOLFOX-6\]). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive either irinotecan hydrochloride over 1 hour or oxaliplatin over 1 hour on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil IV over 46 hours continuously beginning on day 1.
* Arm II: Patients receive combination chemotherapy as in arm I and bevacizumab IV on day 1.
Treatment in both arms repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Existing formalin-fixed paraffin-embedded tumor tissue samples are assessed for pharmacogenomics and markers predictive of response, resistance to, or toxicity from bevacizumab. Samples are analyzed via RT-PCR, array comparative genomic hybridization, fluorescence in situ hybridization, sequencing of candidate genes, and immunohistochemistry.
After completion of study treatment, patients are followed for 1 year.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 184
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm II leucovorin calcium Patients receive combination chemotherapy as in arm I and bevacizumab IV on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm II bevacizumab Patients receive combination chemotherapy as in arm I and bevacizumab IV on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm I leucovorin calcium Patients receive either irinotecan hydrochloride over 1 hour or oxaliplatin over 1 hour on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil IV over 46 hours continuously beginning on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm I fluorouracil Patients receive either irinotecan hydrochloride over 1 hour or oxaliplatin over 1 hour on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil IV over 46 hours continuously beginning on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm I irinotecan hydrochloride Patients receive either irinotecan hydrochloride over 1 hour or oxaliplatin over 1 hour on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil IV over 46 hours continuously beginning on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm II fluorouracil Patients receive combination chemotherapy as in arm I and bevacizumab IV on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm I oxaliplatin Patients receive either irinotecan hydrochloride over 1 hour or oxaliplatin over 1 hour on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil IV over 46 hours continuously beginning on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm II irinotecan hydrochloride Patients receive combination chemotherapy as in arm I and bevacizumab IV on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm II oxaliplatin Patients receive combination chemotherapy as in arm I and bevacizumab IV on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free survival last progression of the last patient
- Secondary Outcome Measures
Name Time Method Response rate last visit of the last patient Overall survival the end of the stady Safety the end of the study
Trial Locations
- Locations (21)
Ospedale Santa Croce
🇮🇹Cuneo, Italy
Ospedale degli Infermi - ASL 12
🇮🇹Biella, Italy
Azienda Usl 8 Arezzo
🇮🇹Arezzo, Italy
Universita Politecnica Delle Marche
🇮🇹Ancona, Italy
A. Perrino Hospital
🇮🇹Brindisi, Italy
Ospedale E. Profili
🇮🇹Fabriano, Italy
Azienda Ospedaliera S. Elia
🇮🇹Caltanissetta, Italy
Ospedale San Giuseppe
🇮🇹Empoli, Italy
Azienda Ospedaliero Careggi
🇮🇹Florence, Italy
Ospedale Civile S. Croce
🇮🇹Fano, Italy
Azienda Ospedaliera di Firenze
🇮🇹Florence, Italy
Ospendale S. Andrea EST
🇮🇹La Spezia, Italy
Azienda USL12 Versilia
🇮🇹Lido di Camaiore, Italy
Ospedale Campo Di Marte Lucca
🇮🇹Lucca, Italy
Istituto Nazionale per la Ricerca sul Cancro
🇮🇹Genoa, Italy
Azienda Ospedaliera Maggiore Della Carita
🇮🇹Novara, Italy
Azienda Ospedaliera Vito Fazzi
🇮🇹Lecce, Italy
Azienda Ospedaliera Pisana
🇮🇹Pisa, Italy
Arcispedale S. Maria Nuova
🇮🇹Reggio Emilia, Italy
Azienda Ospedaliera Universitaria Senese
🇮🇹Siena, Italy
Dipartimento Oncologico
🇮🇹Siena, Italy