Combination Chemotherapy and Cetuximab or Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, oxaliplatin, capecitabine, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different combinations may kill more tumor cells. Monoclonal antibodies, such as bevacizumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy together with bevacizumab or cetuximab may kill more tumor cells.

PURPOSE:To evaluate the use of standard (KRAS) and experimental (thymidine phosphorylase, ERCC1 and BRAF) tumor testing can aid in selecting chemotherapy regimens

PRIMARY OBJECTIVES:

I. To evaluate the feasibility, as defined by completion of three specific marker assays and generation of clinically meaningful endpoints, of selecting treatment regimen components based on biologic tumor characteristics in chemotherapy-naïve patients with metastatic colorectal cancer.

SECONDARY OBJECTIVES:

I. To investigate the response rate associated with genotype/phenotype guided therapy using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

II. To investigate the time to failure of treatment strategy associated with genotype/phenotype guided therapy, defined as the time from initiation of investigational treatment strategy until death, disease progression, initiation of a new therapeutic agent, or disease progression while on a partial or complete treatment holiday.

III. To investigate the progression-free survival associated with genotype/phenotype guided therapy, defined as the time from enrollment to time of progression of disease or death.

OUTLINE: Patients are assigned to treatment groups based on marker assay results.

ARM A: TP-/uncertain, KRAS and BRAF wild-type, ERCC1 high ARM B: TP-/uncertain, KRAS and BRAF wild-type, ERCC1 low/uncertain ARM C: TP-/uncertain, KRAS or BRAF mutant/uncertain, ERCC1 high ARM D: TP-/uncertain, KRAS or BRAF mutant/uncertain, ERCC1 low/uncertain ARM E: TP+, KRAS and BRAF wild-type, ERCC1 high ARM F: TP+, KRAS and BRAF wild-type, ERCC1 low/uncertain ARM G: TP+, KRAS or BRAF mutant/uncertain, ERCC1 high ARM H: TP+, KRAS or BRAF mutant/uncertain, ERCC1 low/uncertain ARM I: TP uninterpretable, KRAS or BRAF uninterpretable, ERCC1 uninterpretable

KRAS testing is standard of care in patients with metastatic colorectal cancer; tymidine phosphorylase, ERCC1 and BRAF testing assays are still experimental.

Courses in arms A-D and arm I repeat every 28 days and courses in arms E-H repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 18 months.

Eligibility Criteria:
Inclusion Criteria:

* Patients must have histologically confirmed colon or rectal cancer that has metastasized; no biopsy of metastatic site(s) are required if presentation is consistent with metastatic disease
* Available archived tissue block or slides from the primary colon or rectal cancer; approximately 25 slides from the primary tumor tissue are necessary for testing of all markers
* Patients must have measurable disease by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm with computed tomography (CT) scan or clinical exam with calipers; lymph nodes must be 15 mm in shortest dimension as measured on CT scan
* Patients may not have received prior therapy for metastatic colorectal cancer; prior adjuvant therapy (including any of the study agents) is permitted if completed \> 6 months from the initial detection of metastatic disease
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 2 X institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 3 X institutional ULN or =\< 5 X ULN if known liver metastases
* Creatinine clearance \>= 50 mL/min (as calculated by Cockroft and Gault formula)
* Urine protein:creatinine (UPC) ratio \< 1.0 at screening (as calculated from urine protein concentration and urine creatinine concentration); patients with a UPC ratio \>= 1 will undergo a 24-hour urine collection, which must be adequate and demonstrate \< 1 gram in order to participate
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients who have had previous chemotherapy for metastatic colorectal cancer
* Uncontrolled hypertension (\>150/100 mmHg) despite a stable regimen of anti-hypertensive medication
* History of cardiovascular disease, defined as previous myocardial infarction, cerebrovascular accident, uncontrolled congestive heart failure (New York Heart Association \> Class II), clinically significant ventricular arrhythmia requiring medication, clinically significant peripheral vascular disease, or unstable angina within 6 months of study enrollment
* Underlying neuropathy \>= grade 2
* Serious non-healing wounds, ulcers, or fistulas
* Major surgery, open biopsy, or major traumatic injury within 28 days of registration, or anticipation of need for surgical procedure during course of study, and core biopsy or fine needle aspiration within 7 days of registration; closed biopsy or access port placement is acceptable
* A history of thrombotic or hemorrhagic disorder; patients with elevated international normalized ratio (INR) (2.0 to 3.0) on stable doses of therapeutic anticoagulation are eligible
* Untreated brain metastases; patients with treated brain metastases who have completed radiation therapy, are clinically and radiographically stable, and are off steroid therapy may be enrolled
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab, oxaliplatin, capecitabine, or other agents used in the study
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded; breastfeeding should be discontinued if the mother is treated with chemotherapy
* Human Immunodeficiency Virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
* Patients must not have a history of another neoplasm \< 5 years prior to enrollment, except for non-metastatic, non-melanoma skin cancer or carcinoma in situ of the cervix
* Patients of child-bearing potential who are unwilling or unable to utilize contraceptive measures including barrier contraception