Combination Chemotherapy Plus Bevacizumab With or Without Oxaliplatin in Treating Older Patients With Metastatic Colorectal Cancer

This randomized phase III trial studies how well combination chemotherapy plus bevacizumab with or without oxaliplatin works in treating older patients with colorectal cancer that has spread to other places in the body. Drugs used in chemotherapy 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) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. Bevacizumab may also stop the growth of cancer by blocking blood flow to the tumor. It is not yet known whether combination chemotherapy plus bevacizumab is more effective with or without oxaliplatin in treating colorectal cancer.

PRIMARY OBJECTIVES:

I. To compare the progression-free survival (PFS) of elderly patients with metastatic colorectal carcinoma who are randomized to receive fluoropyrimidine (fluorouracil)-based therapy plus bevacizumab, with or without oxaliplatin.

SECONDARY OBJECTIVES:

I. In a prospectively planned pooled analysis with a similar trial to be conducted by the Japanese Clinical Oncology Group (JCOG), evaluate and compare the overall survival (OS) of elderly patients with metastatic colorectal carcinoma who are randomized to receive fluoropyrimidine-based therapy plus bevacizumab, with or without oxaliplatin.

II. To assess and compare response rates and adverse events of elderly patients with metastatic colorectal carcinoma randomized to receive fluoropyrimidine-based therapy plus bevacizumab, with or without oxaliplatin.

OUTLINE: Patients are randomized to 1 of 2 treatment arms and assigned to treatment groups based on physician decision for fluoropyrimidine.

ARM A: Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 5 years.

Eligibility Criteria:
Inclusion Criteria

* Patients must have metastatic colorectal cancer that has been histologically or cytologically confirmed; Note: histologic confirmation can be obtained from the primary tumor with appropriate imaging studies confirming metastatic spread
* Eastern Cooperative Oncology Group performance status (ECOG PS) 0, 1, or 2
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Peripheral platelet count (PLT) \>= 100,000/mm\^3
* Hemoglobin (HgB) \> 9.0 g/dL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Aspartate transaminase (AST) =\< 2.5 x ULN (=\< 5 x ULN for patients with liver involvement)
* Alkaline phosphatase =\< 3 x ULN (=\< 5 x ULN for patients with liver involvement)
* Creatinine =\< 1.5 x ULN
* International normalized ratio (INR) \< 1.5 x ULN unless patients are receiving anti-coagulation therapy; patients receiving prophylactic anti-coagulation therapy with an agent such as warfarin or heparin are allowed to participate if INR =\< 3.0
* Urine protein creatinine (UPC) ratio \< 1 or urine dipstick \< 2+

  \* NOTE: Urine protein must be screened by urine analysis for urine protein creatinine (UPC) ratio or by dip stick; for UPC ratio \>= 1.0 or urine dipstick \>= 2+, 24-hour urine protein must be obtained and the level should be \< 1000 mg
* Life expectancy \>= 3 months
* Ability to complete questionnaire(s) by themselves or with assistance
* Provide informed written consent
* Willing to provide mandatory blood samples for correlative research purposes

Exclusion Criteria

* Men of child bearing potential who are unwilling to employ adequate contraception
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of the safety and adverse events of the prescribed regimens
* Immunocompromised patients (other than that related to the use of corticoid steroids) including patients known to be human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 \< 100 cells/uL
* 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
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
* Other active malignancy =\< 3 years prior to randomization; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, patients must not be receiving other specific treatment (other than hormonal therapy) for this prior cancer
* Prior chemotherapy, radiation therapy, immunotherapy, or biological therapy for recurrent or metastatic colorectal cancer

  \* NOTE: prior chemotherapy or radiotherapy is permitted if they had been administered as adjuvant or neoadjuvant therapy and a complete surgical resection of the original colorectal cancer had been achieved
* Progressive disease =\< 12 months of completing oxaliplatin-containing adjuvant therapy
* Prior radiation to \> 30% of the bone marrow at any time
* Calculated creatinine clearance \< 60 mL/minute

  \* NOTE: If calculated creatinine clearance does not meet eligibility requirement, a 24-hour urine can be collected for a creatinine clearance, and the patient can been rolled if measured creatinine clearance \>= 60 mL/minute
* Known central nervous system or brain metastasis that are either symptomatic or untreated; Note: if a patient has a resection of the metastasis and is no longer symptomatic, the patient is eligible for the study; Note: patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis
* New York Heart Association (NYHA) classification III or IV congestive heart failure
* Inadequately controlled hypertension (systolic blood pressure of \> 150 mm Hg or diastolic blood pressure \> 100 mm Hg on anti-hypertensive medications)
* Major surgical procedures, open biopsy or significant traumatic injury =\< 28 days prior to randomization or anticipation of need for elective or planned major surgical procedure during the course of the study
* Core biopsy or other minor surgical procedures =\< 7 days prior to randomization

  \* NOTE: Placement of a vascular access device is allowed
* Active or recent hemoptysis (\>= ½ teaspoon of bright red blood per episode) =\< 30 days prior to randomization
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =\< 6 months prior to randomization
* Serious non-healing wound, active ulcer, or untreated bone fracture

  \* NOTE: patients with fractures secondary to metastatic disease are eligible after appropriate radiotherapy
* History of hypertensive crisis or hypertensive encephalopathy
* Patient has experienced any arterial thromboembolic events including, but not limited to myocardial infarction, stroke, transient ischemic attack (TIA), cerebrovascular accident, unstable angina =\< 6 months prior to randomization or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
* Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis =\< 6 months prior to randomization
* Evidence or history of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation) any hemorrhage/bleeding event \> grade 3 =\< 4 weeks prior to randomization; patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose, at least 2 weeks, of low molecular weight heparin or warfarin and has an INR range 2-3; aspirin doses \> 325 mg daily are not allowed
* Known hypersensitivity to any of the components of 5-fluorouracil/leucovorin, capecitabine, oxaliplatin, or bevacizumab
* Clinically significant peripheral neuropathy at the time of randomization (defined in the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]4.0 as \>= grade 2 neurosensory or neuromotor toxicity)