Phase II Trial of FOLFOX6, Bevacizumab and Cetuximab in Patients With Colorectal Cancer

Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the colon or rectum which is beyond the scope of surgical resection (MEDRA code:"Colorectal neoplasms malignant","Colorectal cancer stage IV","10010035")
* Measurable disease,
* Life expectancy of greater than 3 months
* ECOG performance status =\< 1
* Leukocytes \>= 3,500/uL
* Absolute neutrophil count \>= 1,500/uL
* Platelets \>= 150,000/uL
* Total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal
* Creatinine within normal institutional limits
* Patients may not have received prior therapy with bevacizumab or cetuximab
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to radiotherapy administered more than 4 weeks earlier
* Patients may not be receiving any other investigational agents
* Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in the study
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant or lactating women
* Serious or non-healing wound, ulcer or bone fracture
* Invasive procedures defined as follows:

  * Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
  * Anticipation of need for major surgical procedures during the course of the study
  * Core biopsy within 7 days prior to D1 therapy
* If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment:

  * The subject must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin
  * The subject must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices)
* Active infection requiring parental antibiotics on D1
* Proteinuria at baseline; subjects unexpectedly discovered to have \>= 1+ proteinuria will undergo a 24-hour urine collection, which will be \< 1000 mg protein/ 24 hours to be allowed participation in the study
* No currently active second malignancy other than non-melanoma skin cancer or carcinoma in-situ of the cervix; patients are not considered to have a "currently active" malignancy if they have completed therapy and have no evidence of recurrence for at least 5 years
* Patients with clinically significant cardiovascular disease:

  * Uncontrolled hypertension
  * Myocardial infarction or unstable angina \< 6 months prior to registration
  * New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris
  * Grade II or greater peripheral vascular disease
  * CVA within 6 months of study entry