Study of Oxaliplatin, Capecitabine and Bevacizumab as First Line Treatment for Patients With Advanced Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Oxaliplatin; Bevacizumab; Capecitabine
Intervention MeSH terms: Bevacizumab; Capecitabine; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: colorectal; cancer

Summary:

      This study is for people with colorectal cancer, who have tumors that cannot be completely
      removed by surgery. This study is being done to find out how long it takes tumors to grow
      after patients receive the drugs capecitabine, oxaliplatin and bevacizumab. Capecitabine
      (also called Xeloda) is a drug that has been approved by the FDA for treatment of advanced
      colorectal cancer. Capecitabine prevents some colorectal cancer cancer cells from
      reproducing, and causes some of them to die. Oxaliplatin (also called Eloxatin) has also been
      approved by the FDA for treatment of advanced colorectal cancer. Oxaliplatin prevents some
      colorectal cancer cells from reproducing. Bevacizumab is an investigational drug. Bevacizumab
      is an antibody (a protein that acts against a specific substance) directed against vascular
      endothelial growth factor (VEGF). VEGF promotes the growth of blood vessels that bring
      nutrients to cells. Bevacizumab inhibits the growth of colon cancer cells, by blocking the
      effects of VEGF. The combination of the drugs used in this study is experimental. The purpose
      of this study is to see how long it takes patients' tumors to grow when they are taking this
      combination of drugs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed metastatic or recurrent colorectal tumors
             with no previous treatment for advanced disease.

          -  Age greater than or equal to 18 years

          -  SWOG performance status 0-1.

          -  At least one measurable lesion according to the RECIST criteria which has not been
             irradiated (i.e. newly arising lesions in previously irradiated areas are accepted).
             Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by
             conventional techniques.

          -  Have a negative serum pregnancy test within 7 days prior to initiation of chemotherapy
             (female patients of childbearing potential).

          -  Availability of tumor biopsy (paraffin embedded or fresh frozen) at the time of
             diagnosis and/or prior to study entry is required.

          -  Patients must agree to have a 20 cc blood sample drawn in addition to routine labs
             with each cycle of chemotherapy.

        Exclusion Criteria:

          -  Pregnant or lactating woman.

          -  Life expectancy < 3 months.

          -  Serious, uncontrolled, concurrent infection(s) or illness(es)

          -  Any prior oxaliplatin treatment, with the exception of adjuvant therapy given > 12
             months prior to the beginning of study therapy

          -  Prior unanticipated severe reaction to fluoropyrimidine therapy, known
             hypersensitivity to 5-fluorouracil, or known DPD deficiency

          -  Prior unanticipated severe reaction or hypersensitivity to platinum based compounds.

          -  Treatment for other carcinomas within the last five years, except cured non-melanoma
             skin and treated in-situ cervical cancer.

          -  Current, recent (within 4 weeks of first infusion on this study) or planned
             participation in an investigational drug study.

          -  Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic
             coronary artery disease and cardiac arrhythmias not well controlled with medication)
             within the last 6 months.

          -  History of clinically significant interstitial lung disease and/or pulmonary fibrosis.

          -  History of persistent neurosensory disorder including but not limited to peripheral
             neuropathy.

          -  Presence of central nervous system or brain mets.

          -  Major surgery, open biopsy, or significant traumatic injury within 28 days prior to
             Day 0, or anticipation of need for major surgical procedure during the course of the
             study.

          -  Lack of physical integrity of the upper gastrointestinal tract or malabsorption
             syndrome.

          -  Any of the following laboratory values:

               -  Abnormal hematologic values (neutrophils < 1.5 x 109/L, platelet count < 100 x
                  109/L)

               -  Urine protein: creatinine ratio >/= 1.0 Impaired renal function with estimated
                  creatinine clearance < 30 ml/min as calculated with Cockroft et Gault equation:

               -  Serum bilirubin > 1.5 x upper normal limit. ALT, AST > 2.5 x upper normal limit
                  (or > 5 x upper normal limit in the case of liver metastases)

               -  Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in
                  the case of liver metastases or > 10 x upper normal limit in the case of bone
                  disease)

          -  Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
             prior to Day 0

          -  Blood pressure > 150/100 mmHg

          -  Unstable angina

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  History of myocardial infarction or stroke within 6 months

          -  Clinically significant peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess
             within 28 days prior to Day 0.

          -  Serious, non-healing wound, ulcer or bone fracture

          -  Carcinoma of any histology in close proximity to a major vessel, cavitation or history
             of hemoptysis.

          -  Completion of previous adjuvant chemotherapy regimen < four weeks prior to the start
             of study treatment (within six weeks of study treatment for mitomycin C and
             nitroureas), or with related toxicities unresolved prior to the start of study
             treatment.