Phase II Trial of FOLFOX6, Bevacizumab and Cetuximab in Patients With Colorectal Cancer
Condition: Adenocarcinoma of the Rectum; Mucinous Adenocarcinoma of the Colon; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Stage IV Colon Cancer; Stage IV Rectal Cancer
MeSH terms: Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Recurrence
Intervention: cetuximab; bevacizumab; oxaliplatin; leucovorin calcium; fluorouracil
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Leucovorin; Bevacizumab; Antineoplastic Agents, Immunological; Cetuximab; Fluorouracil; Oxaliplatin; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Drugs used in chemotherapy 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 and cetuximab, 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 combination chemotherapy together with
      bevacizumab and cetuximab may kill more tumor cells. This phase II trial is studying how well
      giving combination chemotherapy together with bevacizumab and cetuximab works in treating
      patients with stage IV colorectal cancer that cannot be removed by surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the colon or rectum which
             is beyond the scope of surgical resection (MEDRA code:"Colorectal neoplasms
             malignant","Colorectal cancer stage IV","10010035")

          -  Measurable disease,

          -  Life expectancy of greater than 3 months

          -  ECOG performance status =< 1

          -  Leukocytes >= 3,500/uL

          -  Absolute neutrophil count >= 1,500/uL

          -  Platelets >= 150,000/uL

          -  Total bilirubin within normal institutional limits

          -  AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

          -  Creatinine within normal institutional limits

          -  Patients may not have received prior therapy with bevacizumab or cetuximab

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had radiotherapy within 4 weeks prior to entering the study or those
             who have not recovered from adverse events due to radiotherapy administered more than
             4 weeks earlier

          -  Patients may not be receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to any of the agents used in the study

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant or lactating women

          -  Serious or non-healing wound, ulcer or bone fracture

          -  Invasive procedures defined as follows:

               -  Major surgical procedure, open biopsy or significant traumatic injury within 28
                  days prior to Day 1 therapy

               -  Anticipation of need for major surgical procedures during the course of the study

               -  Core biopsy within 7 days prior to D1 therapy

          -  If a patient is on full-dose anticoagulants, the following criteria should be met for
             enrollment:

               -  The subject must have an in-range INR (usually between 2 and 3) on a stable dose
                  of warfarin or on stable dose of LMW heparin

               -  The subject must not have active bleeding or pathological conditions that carry
                  high risk of bleeding (e.g. tumor involving major vessels, known varices)

          -  Active infection requiring parental antibiotics on D1

          -  Proteinuria at baseline; subjects unexpectedly discovered to have >= 1+ proteinuria
             will undergo a 24-hour urine collection, which will be < 1000 mg protein/ 24 hours to
             be allowed participation in the study

          -  No currently active second malignancy other than non-melanoma skin cancer or carcinoma
             in-situ of the cervix; patients are not considered to have a "currently active"
             malignancy if they have completed therapy and have no evidence of recurrence for at
             least 5 years

          -  Patients with clinically significant cardiovascular disease:

               -  Uncontrolled hypertension

               -  Myocardial infarction or unstable angina < 6 months prior to registration

               -  New York heart association grade II or greater congestive heart failure, serious
                  cardiac arrhythmia requiring medication, unstable angina pectoris

               -  Grade II or greater peripheral vascular disease

               -  CVA within 6 months of study entry