500 Boylston Street, Boston, MA 02116 617-419-4700
Return to Results
RATIONALE: Monoclonal antibodies, such as cetuximab and 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. Cetuximab may also
stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.
Drugs used in chemotherapy, such as fluorouracil, leucovorin, oxaliplatin, and irinotecan,
work in different ways to stop the growth of tumor cells, either by killing the cells or by
stopping them from dividing. Giving monoclonal antibodies together with combination
chemotherapy may kill more tumor cells. It is not yet known whether combination chemotherapy
is more effective with cetuximab and/or bevacizumab in treating patients with colorectal
PURPOSE: This randomized phase III trial is studying cetuximab and/or bevacizumab when given
together with combination chemotherapy to compare how well they work in treating patients
with metastatic colorectal cancer.
Active, not recruiting
Ages:18 and older
DISEASE CHARACTERISTICS: - Histologically or cytologically confirmed adenocarcinoma of the colon or rectum - Locally advanced (unresectable) or metastatic disease - Patients with resected primary tumors who have documented metastases are eligible - Separate histological or cytological confirmation is not required from patients with a history of colorectal cancer (previously treated by surgical resection) who have now developed radiological or clinical evidence of metastatic disease, unless 1 of the following is true: - An interval of > 5 years has elapsed between the primary surgery and the development of metastatic disease - The primary cancer was stage I - Patient must have a wildtype K-ras gene determined by the SWOG Solid Tumor Repository laboratory or by local CLIA-certified laboratory - Patients with a mutation in the K-ras gene not allowed - The intent of this treatment must be indicated as follows: - Palliative or neoadjuvant treatment with the potential for resection of all sites of metastatic disease - At least 1 paraffin block of previously resected primary tumor or tumor deposit available - Patients must have a wildtype K-ras gene - No known CNS metastases or carcinomatous meningitis PATIENT CHARACTERISTICS: Performance status - ECOG 0-1 Life expectancy - Not specified Hematopoietic - Granulocyte count ≥ 1,500/mm^3 - Platelet count ≥ 100,000/mm^3 - Hemoglobin ≥ 9.0 g/dL (transfusion allowed) - No history of significant bleeding episodes (e.g., hemoptysis or upper or lower gastrointestinal bleeding) within the past 6 months unless the source of bleeding has been resected Hepatic - Bilirubin ≤ 1.5 mg/dL - Albumin ≥ 2.5 g/dL - No evidence of Gilbert's syndrome for patients assigned to receive FOLFIRI chemotherapy - Gilbert's syndrome allowed for patients assigned to receive FOLFOX chemotherapy Renal - Creatinine ≤ 1.5 times upper limit of normal - Protein < 1+ by urinalysis - Protein < 1 g by 24-hour urine collection for patients with protein ≥ 2+ by urinalysis Cardiovascular - No arterial thromboembolic events within the past 6 months, including any of the following: - Myocardial infarction - Transient ischemic attack - Cerebrovascular accident - Unstable angina or angina requiring surgical or medical intervention - No uncontrolled hypertension (i.e., blood pressure ≥ 160/90 on a regimen of antihypertensive therapy) - No New York Heart Association class II-IV congestive heart failure - No clinically significant peripheral artery disease (i.e., claudication on less than 1 block) Pulmonary - No interstitial pneumonia - No extensive or symptomatic interstitial fibrosis of the lung - No pleural effusion or ascites that causes ≥ grade 2 dyspnea Gastrointestinal - No gastrointestinal perforation within past year - No uncontrolled, predisposing colonic or small bowel disorder (i.e., > 3 watery or soft stools daily for patients without a colostomy or ileostomy) - Patients with a colostomy or ileostomy are eligible at the discretion of the investigator Neurologic - No sensory peripheral neuropathy ≥ grade 2 for patients assigned to receive FOLFOX chemotherapy - No uncontrolled seizure disorder - No active neurological disease Other - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for at least 2-6 months after completion of study treatment - No serious nonhealing wound, ulcer, or bone fracture - No known hypersensitivity to Chinese hamster ovary cell products or recombinant human or murine antibodies - No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy - No prior agents that target vascular endothelial growth factor (VEGF) or EGF receptors including protein products, monoclonal antibodies, or antisense therapies - No prior bevacizumab or cetuximab - No concurrent prophylactic filgrastim (G-CSF), pegfilgrastim, or sargramostim (GM-CSF) Chemotherapy - See Radiotherapy - More than 12 months since prior adjuvant chemotherapy (≤ 6 months in duration) that included fluorouracil alone or in combination with oxaliplatin or irinotecan hydrochloride - No prior regional chemotherapy (e.g., hepatic arterial infusion) - No other concurrent chemotherapy Endocrine therapy - No concurrent hormonal therapy except steroids for adrenal failure, hormones for noncancer-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic Radiotherapy - Prior radiotherapy with radiosensitizing chemotherapy allowed - Prior standard adjuvant chemoradiotherapy for rectal cancer allowed - At least 4 weeks since prior radiotherapy - No prior radiotherapy to > 25% of bone marrow - No concurrent palliative radiotherapy except whole brain irradiation for documented CNS disease Surgery - See Disease Characteristics - At least 4 weeks since prior major surgery - At least 2 weeks since prior minor surgery - Insertion of a vascular access device is not considered a prior surgery - Recovered from all prior surgery Other - At least 4 weeks since prior itraconazole or ketoconazole - No prior tyrosine kinase inhibitor therapy - No prior systemic treatment for advanced or metastatic colorectal cancer - No concurrent aprepitant - Concurrent full-dose anticoagulation (i.e., warfarin) allowed provided all of the following criteria are met: - In-range INR (usually 2-3) on a stable dose of oral anticoagulant or stable dose of low molecular weight heparin - No active bleeding - No pathological condition with a high risk of bleeding (e.g., tumor involving major vessels or known varices) - Concurrent antiplatelet agents allowed - Concurrent daily prophylactic aspirin or anticoagulation for atrial fibrillation allowed
Sponsor: Cancer and Leukemia Group B
Phase: Phase 3
Trial ID: NCT00265850
Not Accepting Healthy Volunteers