Sorafenib and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

You may be eligible if

• 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) \< 1.5 (≤ 3.0 if on anti-coagulation therapy \[e.g., warfarin or heparin\])
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 times ULN (≤ 5 times ULN if there is liver involvement)
• Alkaline phosphatase ≤ 3 times ULN
• Creatinine ≤ 1.5 times ULN
• Urine protein:creatinine ratio \< 1 OR urine dipstick \< 2+ OR urine protein \< 1,000 mg by 24-hour urine collection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment (≥ 2 weeks after completion of treatment with sorafenib tosylate alone)
• Willing to provide mandatory blood samples for translational research studies
• Able to swallow whole pills
• No inadequately controlled hypertension (i.e., systolic BP \> 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