Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: bevacizumab; fluorouracil; irinotecan hydrochloride; leucovorin calcium; polymorphism analysis
Intervention MeSH terms: Leucovorin; Bevacizumab; Fluorouracil; Irinotecan; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage IV colon cancer; stage IV rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum; recurrent colon cancer; recurrent rectal cancer

Summary:

      RATIONALE: Monoclonal antibodies, such as 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. Bevacizumab may also stop the
      growth of colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy,
      such as irinotecan, leucovorin, and fluorouracil, work in different ways to stop the growth
      of tumor cells, either by killing the cells or by stopping them from dividing. Giving
      bevacizumab together with combination chemotherapy may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving bevacizumab together with
      combination chemotherapy works as first-line therapy in treating patients with metastatic
      colorectal cancer that cannot be removed by surgery.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed adenocarcinoma of the colon or rectum

               -  No other histological types

          -  Metastatic, unresectable disease

               -  No bone metastases only

          -  Unidimensionally measurable metastatic disease

          -  No CNS metastases

        PATIENT CHARACTERISTICS:

          -  WHO performance status (PS) 0-2 OR Karnofsky PS 70-100%

          -  Life expectancy ≥ 12 weeks

          -  ANC > 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 10 g/dL

          -  Bilirubin ≤ 1.25 times normal (1.5 times normal in presence of hepatic metastases)

          -  AST and ALT < 3 times normal (5 times normal in presence of hepatic metastases)

          -  Creatinine < 1.25 times normal

          -  No proteinuria

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No other cancer in the past 5 years except for carcinoma in situ of the uterine cervix
             or basal cell skin cancer

          -  No hypersensitivity to fluorouracil

          -  No hypersensitivity to leucovorin calcium, bevacizumab, or their excipients

          -  No hypersensitivity to Chinese hamster ovarian cell products or other recombinant
             humanized or nonhumanized monoclonal antibodies

          -  No allergy to irinotecan hydrochloride

          -  No prior reaction to attenuated vaccines (fever, jaundice)

          -  No poor nutritional status

          -  No Biermer anemia or other anemia due to vitamin B12 deficiency

          -  No uncontrolled symptomatic occlusion or subocclusion

          -  No medullary hypoplasia or severe insufficiency

          -  No prior chronic intestinal disease

          -  No Gilbert's syndrome

          -  No intra-abdominal inflammatory reaction (e.g., gastroduodenal ulcer, diverticulitis,
             or colitis)

          -  No chronic intestinal inflammatory disease

          -  No thromboembolic arterial condition in the past 6 months, including any of the
             following:

               -  Cardiovascular accident

               -  Transient ischemic attack

               -  Myocardial infarction

          -  No infection or serious noncancerous disease

          -  No condition that is unstable or would increase risk to the patient, including any of
             the following:

               -  Unstable angina

               -  Poorly controlled hypertension

               -  Severe cardiac insufficiency

               -  Serious arrhythmia

               -  Bleeding diathesis

               -  Pulmonary disease at risk of decompensation

          -  No familial, geographical, social, or psychological condition that would preclude
             study participation

          -  No prisoners or patients without guardians

        PRIOR CONCURRENT THERAPY:

          -  At least 8 weeks since prior surgery

          -  At least 6 months since prior adjuvant chemotherapy

          -  At least 1 month since prior palliative chemotherapy

          -  No prior abdominal or pelvic radiotherapy

          -  At least 30 days since prior participation in another investigational study

          -  No prior bevacizumab

          -  No extensive intestinal resection (e.g., partial colectomy or extensive thin
             resection)

          -  No concurrent warfarin, Hypericum perforatum (St. John's wort), or prophylactic
             phenytoin