Second-Line Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer Who Have Received First-Line Chemotherapy and Bevacizumab (BEBYP)
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring adenocarcinoma of the colon, adenocarcinoma of the rectum, recurrent colon cancer, recurrent rectal cancer, stage IV colon cancer, stage IV rectal cancer, stage III rectal cancer, stage III colon cancer
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed colorectal adenocarcinoma
- Metastatic or unresectable disease
Progressive disease based on the following criteria:
Progression during or after first-line chemotherapy for metastatic disease, including any of the following:
- Fluoropyrimidine-based monotherapy with bevacizumab
- Fluoropyrimidine and irinotecan hydrochloride-based doublet with bevacizumab
- Fluoropyrimidine and oxaliplatin-based doublet with bevacizumab
- Progression after more than 3 months from the last administration of first-line chemotherapy for metastatic disease with a fluoropyrimidine, irinotecan hydrochloride, and oxaliplatin triplet (FOLFOXIRI) with bevacizumab to which the patient had previously responded
- Measurable disease, as assessed by RECIST criteria
- No prior or concurrent CNS metastasis
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 3 months
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
- INR ≤ 1.5 times upper limit of normal (ULN)
- aPTT ≤ 1.5 ULN
- Serum bilirubin ≤ 1.5 times ULN
- AST and ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
- Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
- Serum creatinine ≤ 1.5 times ULN
- Proteinuria < 2+ OR protein ≤ 1g by 24-hour urine
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No bowel obstruction or subobstruction
- No history of inflammatory enteropathy
- No prior extensive intestinal resection (i.e., > hemicolectomy or extensive small intestine resection with chronic diarrhea)
- No symptomatic peripheral neuropathy > grade 2
- No active uncontrolled infection
- No active disseminated intravascular coagulation
- No prior or concurrent malignancy, except for curatively treated basal cell and squamous cell carcinoma of the skin, or in situ carcinoma of the cervix
No clinically significant cardiovascular disease, including any of the following:
- Cerebrovascular accident within the past 6 months
- Myocardial infarction within the past 6 months
- Unstable angina
- NYHA class II-IV chronic heart failure
- Uncontrolled arrhythmia
- No uncontrolled hypertension
- No thromboembolic or hemorrhagic events within the past 6 months
- No evidence of bleeding diathesis or coagulopathy
- No serious, non healing wound/ulcer or serious bone fracture
- No significant traumatic injury within the past 28 days
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 6 weeks since prior radiotherapy
- At least 4 weeks since prior surgery
- No prior first-line chemotherapy for metastatic disease without bevacizumab
- No prior cetuximab or other investigational agents
- More than 28 days since prior open biopsy
- More than 28 days since prior and no concurrent major surgical procedure
No concurrent therapeutic anticoagulation, antiplatelet agents, or NSAID with anti-platelet activity
- Acetylsalicylic acid ≤ 325 mg/day allowed
Sites / Locations
- Universita Politecnica Delle Marche
- Azienda Usl 8 Arezzo
- Ospedale degli Infermi - ASL 12
- A. Perrino Hospital
- Azienda Ospedaliera S. Elia
- Ospedale Santa Croce
- Ospedale San Giuseppe
- Ospedale E. Profili
- Ospedale Civile S. Croce
- Azienda Ospedaliera di Firenze
- Azienda Ospedaliero Careggi
- Istituto Nazionale per la Ricerca sul Cancro
- Ospendale S. Andrea EST
- Azienda Ospedaliera Vito Fazzi
- Azienda USL12 Versilia
- Ospedale Campo Di Marte Lucca
- Azienda Ospedaliera Maggiore Della Carita
- Azienda Ospedaliera Pisana
- Arcispedale S. Maria Nuova
- Azienda Ospedaliera Universitaria Senese
- Dipartimento Oncologico
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm I
Arm II
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.
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.