Capecitabine, Cetuximab, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer That Cannot Be Removed By Surgery
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: bevacizumab; cetuximab; capecitabine; oxaliplatin
Intervention MeSH terms: Bevacizumab; Cetuximab; Capecitabine; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the colon; recurrent colon cancer; stage IV colon cancer; adenocarcinoma of the rectum; recurrent rectal cancer; stage IV rectal cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, 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 cetuximab and bevacizumab, 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. Cetuximab and bevacizumab
      may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving
      capecitabine together with cetuximab, oxaliplatin, and bevacizumab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving capecitabine together with
      cetuximab, oxaliplatin, and bevacizumab works in treating patients with metastatic or
      recurrent colorectal cancer that cannot be removed by surgery.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed adenocarcinoma of the colon or rectum

               -  Unresectable disease

               -  Metastatic or recurrent disease

          -  Not amenable to potentially curative treatment

          -  No untreated leptomeningeal or brain metastases

        PATIENT CHARACTERISTICS:

        Performance status

          -  ECOG 0-2

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Absolute neutrophil count ≥ 2,000/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  No known uncontrolled coagulopathy

        Hepatic

          -  AST and ALT < 2.5 times upper limits of normal (ULN) (5 times ULN if liver metastases
             are present)

          -  Bilirubin < 2.0 times ULN

        Renal

          -  Creatinine clearance > 40 mL/min

          -  Urine protein negative

          -  Urine protein:creatinine ratio > 1

        Cardiovascular

          -  No unstable or uncontrolled hypertension (i.e., blood pressure [BP] > 150/100 mm Hg
             despite antihypertensive therapy)

               -  Patients who recently started or have adjusted antihypertensive medications are
                  eligible provided BP is < 140/90 mm Hg for ≥ 3 different measurements over 14
                  days

          -  No arterial thromboembolic events within the past 6 months, including any of the
             following:

               -  Transient ischemic attack

               -  Cerebrovascular accident

               -  Unstable angina

               -  Myocardial infarction

               -  Clinically significant peripheral vascular disease

          -  No New York Heart Association class III-IV congestive heart failure

          -  No uncontrolled symptomatic coronary artery disease or cardiac arrhythmia

          -  No other significant uncontrolled cardiac disease

        Gastrointestinal

          -  No lack of physical integrity of the upper gastrointestinal tract

          -  No malabsorption syndrome

          -  No inability to tolerate oral medication

        Immunologic

          -  No prior severe infusion reaction to a monoclonal antibody

          -  No history of an allergic reaction attributed to compounds of similar chemical or
             biologic composition to oxaliplatin, cetuximab, capecitabine, or bevacizumab

          -  No prior unanticipated, severe reaction to fluoropyrimidine therapy or known
             hypersensitivity to fluoroucacil

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during the study and for 3-4 months
             after completion of study treatment

          -  No peripheral neuropathy ≥ grade 2

          -  No other malignancy within the past 5 years except adequately treated nonmelanoma skin
             cancer or carcinoma in situ of the cervix

          -  No known dihydropyrimidine dehydrogenase deficiency

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  No prior adjuvant bevacizumab or cetuximab

          -  No other concurrent anticancer immunotherapy or biologic therapy

        Chemotherapy

          -  At least 6 months since a prior adjuvant fluorouracil-, leucovorin calcium-, or
             capecitabine-based regimen

          -  At least 12 months since prior adjuvant oxaliplatin

          -  No prior chemotherapy for metastatic or recurrent disease

        Endocrine therapy

          -  No concurrent hormonal therapy

        Radiotherapy

          -  No concurrent radiotherapy

        Surgery

          -  More than 4 weeks since prior major surgery and recovered

          -  More than 6 months since vascular surgery, stenting, or angioplasty

        Other

          -  At least 4 weeks since prior and no concurrent sorivudine or brivudine

          -  More than 4 weeks since prior participation in any investigational drug study

          -  No prior therapy that affects or targets the epidermal growth factor pathway

          -  No concurrent cimetidine

               -  Concurrent ranitidine, famotidine, or proton-pump inhibitors allowed

          -  Concurrent anticoagulation therapy with full-dose anticoagulant allowed provided dose
             is stable for at least 2 weeks