Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer
About this trial
This is an interventional treatment trial for Adenocarcinoma of the Colon
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed locally advanced, recurrent, or metastatic colorectal adenocarcinoma Not curable by surgery or amenable to radiotherapy with curative intent Previously resected colorectal cancer with new evidence of metastasis does not require separate histologic or cytologic confirmation unless one of the following is true: More than 5 years has elapsed between primary surgery and development of metastatic disease Primary tumor was T1-T2, N0, M0 Site of primary lesion must be or have been in the large bowel as determined by endoscopy, radiology, or surgery Measurable or evaluable disease No known brain or leptomeningeal disease Performance status - Zubrod 0-2 No history of hemorrhagic or thrombotic disorders Absolute neutrophil count greater than 1,500/mm^3 Platelet count greater than 100,000/mm^3 Bilirubin no greater than 2.0 times upper limit of normal (ULN) SGOT no greater than 2.5 times ULN (5 times ULN for patients with liver involvement) Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN for patients with liver involvement or 10 times ULN for patients with bone involvement) INR no greater than 1.5 PTT no greater than ULN Creatinine no greater than 1.5 times ULN Creatinine clearance at least 50 mL/min Proteinuria less than 1+* Protein less than 500mg/24 hours* No uncontrolled hypertension Hypertension must be well-controlled (i.e., less than 160/90) and on a stable regimen of antihypertensive therapy No unstable angina No symptomatic congestive heart failure No myocardial infarction within the past 6 months No serious uncontrolled cardiac arrhythmia No New York Heart Association class III or IV heart disease No symptomatic pulmonary fibrosis Not pregnant or nursing Fertile patients must use effective contraception No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission No active or uncontrolled severe infection No contraindication to oral medications (e.g., severe dysphagia) G-tubes or J-tubes allowed No peripheral neuropathy greater than grade 1 No serious non-healing wound, ulcer, or bone fracture No significant traumatic injury within the past 28 days No other severe acute or chronic medical condition or laboratory abnormality that would preclude study participation No psychiatric condition that would preclude study participation No prior bevacizumab No prior oxaliplatin No prior chemotherapy for advanced colorectal cancer Prior adjuvant therapy for resected stage II-III disease allowed provided at least 12 months have elapsed between completion of therapy and diagnosis of recurrent disease At least 28 days since prior radiotherapy and recovered See Disease Characteristics More than 28 days since prior major surgical procedure or open biopsy More than 7 days since prior fine needle aspiration or core biopsy No concurrent major surgery More than 10 days since prior full-dose aspirin (325 mg) No concurrent antiplatelet agents (e.g., dipyridamole, ticlopidine, clopidogrel, or cilostazol) No other concurrent investigational agents No concurrent therapeutic anticoagulation Prophylactic anticoagulation of central venous lines allowed Low-dose prophylactic enoxaparin or heparin allowed No concurrent cimetidine No concurrent sorivudine or its related analogs (e.g., brivudine) No concurrent use of a cold cap or iced mouth rinses
Sites / Locations
- Southwest Oncology Group
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm I (oxaliplatin, leucovorin calcium, fluorouracil)
Arm II (oxaliplatin, capecitabine)
Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
Patients receive oxaliplatin IV over 2 hours on day 1and oral capecitabine on days 1-15. Patients are further randomized to receive bevacizumab or placebo* as in arm I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.