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) \< 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