Cetuximab, Bevacizumab & 5FU/Leucovorin vs. Oxaliplatin, Bevacizumab & 5FU/Leucovorin in Metastatic Colorectal Cancer
Condition: Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Bevacizumab; Oxaliplatin; Leucovorin; Fluorouracil; Cetuximab
Intervention description: 5 mg/kg over 30 minutes on Days 1 and 15; 85 mg/m2 on Days 1 and 15; 400 mg/m2 on Days 1 and 15; 400 mg/m2, IV bolus followed by: 1200 mg/m2/day via 24-hour continuous infusion, for 2 consecutive days (total 5-FU infusion dose = 2400 mg/m2 over the 48 hour period); 400 mg/m2 over 2 hours (Cycle 1 Day 1 only) All subsequent doses (Day 8, 15, 22 of Cycle 1 and Days 1, 8, 15, 22 other cycles)250 mg/m2 over 1 hour
Intervention MeSH terms: Leucovorin; Bevacizumab; Cetuximab; Fluorouracil; Oxaliplatin
Phase: Phase 3
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

Summary:

      The purpose of this study is to compare the rates of Progression-Free Survival (PFS) at 12
      months for patients treated with Bev-FOLFOX versus patients treated with FOLF-CB for first
      line treatment of metastatic colorectal cancer.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  Histologically or cytologically confirmed colorectal cancer with metastatic disease

          -  Measurable disease

          -  Previously irradiated lesions will be considered evaluable, if they progressed since
             radiation

          -  Has disease other than limited to surgically resectable liver-only or lung-only
             metastatic disease

          -  Not received prior chemo and/or biotherapy for metastatic disease

          -  Not received oxaliplatin, bevacizumab, or cetuximab in the adjuvant setting

          -  May have received 5-FU, leucovorin, and/or irinotecan in the adjuvant setting, however
             must have remained free of disease recurrence (including free of abnormal CEA level)
             for 1- year or more

          -  Is >18 years of age

          -  ECOG performance status 0 or 1

          -  Normal organ & marrow function

          -  Use of an acceptable method of birth control

          -  Not pregnant or breast feeding

          -  Paraffin tissue block(s) or 12 (minimum) unstained slides available, for assessment of
             potential predictive markers related to the EGFR, VEGF, DNA repair, and
             fluoropyrimidine catabolism pathways. If no block is available, slides (typically 7 to
             10 um sections, air dried on uncharged slides) may be sent

          -  Signed a Patient Informed Consent Form

          -  Signed a Patient Authorization Form (HIPAA) Form

        EXCLUSION CRITERIA:

          -  Had prior chemotherapy for metastatic colorectal cancer

          -  Received any prior treatment with oxaliplatin, bevacizumab, or cetuximab in the
             adjuvant treatment of their colorectal cancer

          -  Currently receiving any other investigational anticancer agents or has participated in
             an experimental drug study within the past 4 weeks

          -  History of primary CNS tumors, seizures not well-controlled with standard medical
             therapy, or stroke

          -  Sustained hypertension, as characterized by persistent blood pressures greater than
             150/100 despite medical management

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure or has
             had angioplasty or placement of coronary stents within the past 6 months

          -  Clinically significant peripheral vascular disease

          -  History of serious allergic reactions attributed to compounds of similar chemical or
             biologic composition to bevacizumab, cetuximab, oxaliplatin, fluorouracil, leucovorin,
             or other agents used in the study

          -  Received prior cetuximab or other EGFR-directed therapy, or history of prior
             anti-cancer murine or chimeric monoclonal antibody therapy; prior humanized and human
             monoclonal antibody therapy is also excluded.

          -  Received prior treatment with bevacizumab or other agents specifically targeting VEGF
             or VEGF receptors

          -  Uncontrolled intercurrent illness including, not limited to, ongoing or active
             infection requiring parenteral antibiotics, symptomatic congestive heart failure,
             uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance with study requirements in the
             opinion of the Investigator/Treating Physician

          -  Serious or non-healing active wound ulcer, or active bone fracture

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 1 of protocol treatment

          -  Minor surgical procedures such as fine needle aspirations or core biopsies within 7
             days prior to Day 1

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to Day 1

          -  Current or recent use of a thrombolytic agent within last 30 days. Use for clearance
             of central line catheter is permitted.

          -  Evidence of bleeding diathesis (disorder) or clinically significant coagulopathy (Note
             that deep venous thrombosis is not regarded as a reason for exclusion from this trial)

          -  Hypersensitivity to Chinese hamster ovary cell products or other recombinant human
             antibodies

          -  History of arterial thromboembolic events within 6 months

          -  Urine protein:creatinine ratio greater than 1.0 at screening

          -  Pregnant or lactating woman

          -  Known to be HIV positive or receiving combination anti-retroviral therapy

          -  Unable to comply with study requirements