Sorafenib and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

Inclusion Criteria

• Diagnosis of stage IV colorectal cancer (histologic proof is not required)
• Measurable disease
• Spiral CT scan required for both pre- and post-treatment tumor assessments of lesions measuring 1-2 cm
• Progressive disease during or within 6 months of most recent prior chemotherapy regimen (bevacizumab, fluoropyrimidine, oxaliplatin, or irinotecan-based treatment) OR considered ineligible for standard therapy
• Documentation of submission of tumor material for Kirsten Rat Sarcoma (KRAS) testing available
• Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab or panitumumab) required for patients with wild-type KRAS tumor
• No known brain metastasis
• Patients with neurological symptoms must undergo a CT scan or MRI of the brain to exclude brain metastasis
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy ≥ 6 months
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• White blood cell count (WBC) ≥ 3,400/mm³
• International normalized ratio (INR) 150 mm Hg or diastolic BP > 100 mm Hg on anti-hypertensive medications)
• No prior hypertensive crisis or hypertensive encephalopathy
• No myocardial infarction or unstable angina within the past 6 months
• No congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months
• No hemorrhage or bleeding event > grade 3 within the past 4 weeks
• No evidence or history of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
• No greater than normal risk of bleeding
• No active or recent hemoptysis (≥ ½ teaspoon of bright red blood per episode) within the past 30 days
• No concurrent uncontrolled illness including, but not limited to, any of the following:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia requiring anti-arrhythmic drugs
• Psychiatric illness or social situations that would limit compliance with study requirements
• No known HIV infection or chronic hepatitis B or C infection
• No serious, non-healing wound, active ulcer, or untreated bone fracture
• Patients with fractures secondary to metastatic disease are eligible after appropriate radiotherapy
• No significant traumatic injury within the past 4 weeks
• No known or suspected allergy or hypersensitivity to any component of bevacizumab, sorafenib tosylate, or their excipients or to any other agent given in the course of this study
• No malabsorption problem
• None of the following within the past 6 months:
• Significant vascular disease (e.g., aortic aneurysm or aortic dissection)
• Peripheral arterial thrombosis
• Symptomatic peripheral vascular disease
• Abdominal fistula
• Gastrointestinal perforation
• Intra-abdominal abscess
• No other active malignancy within the past 3 years except non melanoma skin cancer or carcinoma in situ of the cervix
• Prior malignancy allowed provided patient is not receiving other specific treatment for that malignancy (other than hormonal therapy)
• No other concurrent investigational agent for this cancer
• Prior radiotherapy allowed
• No prior sorafenib tosylate
• No prior discontinuation of bevacizumab due to adverse events
• More than 4 weeks since prior and no concurrent participation in any other experimental drug study
• More than 4 weeks since prior St. John's wort or rifampin
• More than 4 weeks since prior and no concurrent major surgical procedure or open biopsy
• More than 7 days since prior core biopsy or minor surgical procedure, including placement of a vascular access device
• No concurrent anticoagulant, except low-dose warfarin or heparin for deep venous thrombosis prophylaxis