Combination Chemotherapy Plus Bevacizumab With or Without Oxaliplatin in Treating Older Patients With Metastatic Colorectal Cancer
Condition: Cognitive/Functional Effects; Colorectal Cancer; Neurotoxicity
MeSH terms: Colorectal Neoplasms; Neurotoxicity Syndromes
Intervention: bevacizumab; capecitabine; fluorouracil; leucovorin calcium; oxaliplatin
Intervention description: Given IV; Given PO; Given IV; Given IV; Given IV
Intervention MeSH terms: Leucovorin; Bevacizumab; Capecitabine; Fluorouracil; Oxaliplatin; Calcium; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No
Keywords: neurotoxicity; cognitive/functional effects; stage IVA colon cancer; stage IVA rectal cancer; stage IVB colon cancer; stage IVB rectal cancer; recurrent colon cancer; recurrent rectal cancer

Summary:

      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.
    

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)