Cetuximab With or Without Brivanib in Treating Patients With K-Ras Wild Type Tumours and Metastatic Colorectal Cancer

DISEASE CHARACTERISTICS:

* Histologically confirmed primary colorectal cancer

  * Metastatic disease
* Tumor must be confirmed to be K-Ras wild type (i.e., No K-Ras mutation found) by means of mutation analysis performed on representative samples of diagnostic tumor tissue by a central reference laboratory (archival tumor samples are acceptable for K-Ras mutation analysis)
* Must have received a prior thymidylate synthase inhibitor (e.g., fluorouracil, capecitabine, raltitrexed, or tegafur-uracil) for adjuvant and/or metastatic disease

  * Thymidylate synthase inhibitor may have been given in combination with oxaliplatin or irinotecan hydrochloride
* Must meet one of the following criteria:

  * Received and failed\* an irinotecan hydrochloride-containing regimen (i.e., single-agent or in combination) for treatment of metastatic disease
  * Relapsed within 6 months of completion of an irinotecan hydrochloride-containing adjuvant therapy
  * Has documented unsuitability\*\* for an irinotecan hydrochloride-containing regimen NOTE: \*Failure is defined as either progression of disease or intolerance to the irinotecan-containing regimen, where intolerance is defined as discontinuation due to any of the following: severe allergic reaction or delayed recovery from toxicity preventing retreatment NOTE: \*\*Documented unsuitability for irinotecan includes known hypersensitivity to irinotecan, abnormal glucuronidation of bilirubin, Gilbert's syndrome, previous pelvic/abdominal irradiation, or elderly with comorbid conditions
* Must meet one of the following:

  * Received and failed\* an oxaliplatin-containing regimen (i.e. single-agent or in combination) for treatment of metastatic disease
  * Relapsed within 6 months of completion of an oxaliplatin containing adjuvant therapy
  * Has documented unsuitability\*\* for an oxaliplatin-containing regimen NOTE: \*Failure is defined as either progression of disease or intolerance to the oxaliplatin-containing regimen, where intolerance is defined as discontinuation due to any of the following: severe allergic reaction, persistent severe neurotoxicity or delayed recovery from toxicity preventing retreatment

NOTE: \*\*Documented unsuitability for oxaliplatin includes known hypersensitivity to oxaliplatin or other platinum compounds, pre-existing renal impairment, or Grade 2 or greater neurosensory neuropathy

* Measurable or evaluable disease
* Patient must consent to provision of, and investigator(s) must confirm access to and agree to submit at the request of the NCIC CTG Central Tumor Bank, a representative formalin fixed paraffin block of tumour tissue
* Patient must consent to provision of a sample of blood
* No symptomatic CNS metastases

  * Patients with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by CT or MRI scans

PATIENT CHARACTERISTICS:

Inclusion criteria:

* ECOG performance status 0-2
* Absolute granulocyte count ≥ 1.5 x 10\^9/L
* Platelet count ≥ 75 x 10\^9/L
* Hemoglobin ≥ 80 g/L
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (2.0 times ULN with documented liver metastases)
* ALT and AST ≤ 2.5 times ULN (5.0 times ULN with documented liver metastases)
* Serum creatinine ≤ 1.5 times ULN or creatinine clearance \> 50 mL/min
* Magnesium \> 0.5 mmol/L (1.2 mg/dL)
* LVEF \> 45% by ECHO or MUGA scan
* No proteinuria ≥ 2+ on dipstick or ≥ 1 g on 24 hour urine collection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception prior to, during, and for 12 weeks after completion of study treatment
* Able (i.e., sufficiently fluent) and willing to complete the quality of life (EORTC QLQ-C30 and Skindex-16) and health utilities questionnaires (HUI3) in either English or French

Exclusion criteria:

* A history of other malignancies, except: adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
* Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy
* Any condition (e.g., psychological, geographical, etc.) that does not permit compliance with the protocol
* Uncontrolled or significant cardiovascular disease including any of the following:

  * Myocardial infarction within 12 months
  * Uncontrolled angina within 6 months
  * Clinically significant congestive heart failure
  * Stroke, transient ischemic attack, or other ischemic event within 12 months
  * Severe cardiac valve dysfunction
* Uncontrolled hypertension (consistent elevation of systolic BP \> 150 and diastolic BP \> 100 mmHg)
* History of a thromboembolic event in the last 6 months despite being treated with anticoagulation

  * Patients are eligible if they have experienced a thromboembolic event greater than 6 months previously and have initiated and are stable on anticoagulation or if they have previously initiated and are stable on anticoagulation for prevention of thromboembolic events
* Severe restrictive lung disease or radiological pulmonary findings of "interstitial lung disease" on the baseline chest x-ray which, in the opinion of the investigator, represents significant pathology
* Serious non-healing wounds, ulcers, or bone fractures
* History of allergy to brivanib (alaninate or related drug class
* Unable to swallow tablets

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Adequately recovered from recent surgery, chemotherapy and/or radiation therapy
* At least 4 weeks must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or prior radiation therapy
* No prior cetuximab or other therapy\* with targets the EGFR pathway (e.g., erlotinib hydrochloride, gefitinib hydrochloride, panitumumab)
* May have received a single prior regimen which targets the VEGFR pathway (e.g., bevacizumab , vatalanib, AZD2171, sorafenib tosylate, sunitinib malate, or others)
* No prior murine monoclonal antibody therapy (e.g., edrecolomab)
* No other concurrent chemotherapy
* No other concurrent therapies targeting the EGFR pathway (e.g., erlotinib, gefitinib, panitumumab, or others) or other therapies targeting the VEGFR pathway (e.g., bevacizumab , vatalanib, AZD2171, sorafenib tosylate, sunitinib malate, or others)
* Concurrent antihypertensive therapies allowed
* Concurrent aspirin allowed
* No other concurrent noncytotoxic experimental agents