Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: bevacizumab; fluorouracil; irinotecan hydrochloride; leucovorin calcium; Oxaliplatin
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Leucovorin; Tetrahydrofolates; Formyltetrahydrofolates; Bevacizumab; Fluorouracil; Oxaliplatin; Irinotecan; Camptothecin; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 247.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent colon cancer; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum

Summary:

      RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, 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. 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. Giving bevacizumab together with combination chemotherapy may be a better way to block
      tumor growth. Studying the amount of an enzyme found in the tumor may help doctors plan the
      best treatment.

      PURPOSE: This randomized phase II trial is studying giving bevacizumab, oxaliplatin, and
      irinotecan or giving bevacizumab, oxaliplatin, leucovorin, and fluorouracil in treating
      patients with metastatic or recurrent colorectal cancer.
    

Eligibility criteria:

        INCLUSION:

          -  Metastatic or locally recurrent colorectal adenocarcinoma

          -  Measurable disease

          -  At least 2 formalin-fixed paraffin embedded core needle biopsies OR fine needle
             aspirate containing a minimum of 3 clusters of malignant cells and fixed tissue from
             the previous biopsy

          -  If no tissue samples are available the patient must be willing to undergo biopsy of a
             metastatic site

          -  Age 18 and over

          -  Eastern Cooperative Oncology Group (ECOG) Performance status 0-2

          -  Absolute neutrophil count ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Prothrombin time (PT)/international normalized ratio (INR) ≤ 1.5 unless patient is
             receiving full-dose anticoagulants AND the following criteria are met:

               -  In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low
                  molecular weight heparin

               -  No active bleeding or pathological condition that is associated with a high risk
                  of bleeding

          -  Partial thromboplastin time (PTT) < 1.5 times upper limit of normal (ULN)

          -  Alanine transaminase (ALT) and aspartate aminotransferase (AST) < 3 times ULN

          -  Bilirubin ≤ 1.5 times ULN

          -  Creatinine ≤ 1.8 mg/dL

          -  Meets 1 of the following criteria:

               -  Protein negative on urine dipstick

               -  Urine protein/creatinine ratio < 1.0

               -  Less than 2 g protein on 24-hour urine collection

          -  Patients with a history of hypertension must meet the following criteria:

               -  Blood pressure < 150/90 mm Hg

               -  Stable regimen of anti-hypertensive therapy

          -  More than 28 days since prior major or open surgery

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 3 months after study
             participation

          -  Prior non-colorectal malignancies are allowed provided the following criteria are met:

               -  No current clinical evidence of persistent or recurrent disease

               -  No active therapy for non-colorectal malignancy, including hormonal therapy

        EXCLUSION:

          -  Pregnant or nursing

          -  Arterial thromboembolic events within the past 6 months, including the following:

               -  Transient ischemic attack

               -  Cerebrovascular accident

               -  Unstable angina pectoris

               -  Myocardial infarction

          -  Symptomatic arrhythmia

          -  Symptomatic congestive heart failure

          -  Clinically significant peripheral artery disease

          -  New York Heart Association class III or IV heart disease

          -  Serious nonhealing wound, ulcer, or bone fracture within the past 28 days

          -  Significant traumatic injury within the past 28 days

          -  Neuropathy ≥ grade 2

          -  Ongoing or active infection

          -  Concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

          -  Prior chemotherapy for metastatic disease. Adjuvant therapy completed at least 12
             months before first evidence of metastasis allowed

          -  Cardiovascular, renal, hepatic, or other nonmalignant systemic disease that would
             preclude study therapy