Phase II Trial of Neoadjuvant FOLFOX4 and Cetuximab for Localized Adenocarcinoma of Rectum
Condition: Rectal Cancer
MeSH terms: Adenocarcinoma
Intervention: FOLFOX4; Cetuximab
Intervention description: oxaliplatin (85mg/m2 on days 1 and 15 of each cycle)+ 5FU Bolus (400mg/m2 on days 1, 2, 15, and 16 of each cycle) + 5FU CI (600mg/m2 on days 1, 2, 15, and 16 of each cycle) + Leucovorin (200mg/m2 on days 1, 2, 15, and 16 of each cycle); Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study involves the use of Oxaliplatin, 5-Fluorouracil (5-FU), Leucovorin and Cetuximab,
      which are all medicines approved by the Food and Drug Administration (FDA) and are
      commercially available. This treatment regimen will possibly be combined with radiation
      before and/or after surgery depending on your response to the treatment. Their use in this
      exact combination is considered experimental. The purpose of this study is to find out how
      effective this combination of chemotherapy is as treatment for rectal cancer that has not
      spread to other parts of the body. The side effects and survival experienced by subjects
      receiving these drugs will also be evaluated. This is a phase II research study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must have newly diagnosed, histologically proven adenocarcinoma of the
             rectum. Locally advanced T3, T4 or any T with N1, N2, staged by trans-rectal
             ultrasound.

          -  All patients must have an abdominal/pelvis CT scan or MRI confirming no evidence of
             distant metastases.

          -  Patients must have an ECOG PS ≤ 2

          -  Patient has signed informed consent

          -  Lower Age Limit: 18 years

          -  Upper Age Limit: No upper age limit

          -  Laboratory parameters:

               -  Hgb: > 9.0 g/dl

               -  ANC >1500/ul

               -  Platelet >100,000/ul

               -  Creatinine < 2x ULN

               -  Bilirubin < 2x ULN

               -  ALT < 2x ULN

        Exclusion Criteria:

          -  Administration of any prior systemic anticancer therapy for colorectal cancer (eg,
             chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, cytokine
             therapy, angiogenesis inhibitors).

          -  Previous intra-arterial cytotoxic chemotherapy given as treatment for colorectal
             cancer.

          -  Previous pelvic radiotherapy.

          -  Known allergy or intolerance to oxaliplatin, 5-FU, cetuximab or leucovorin.

          -  Pregnant or breast-feeding women: female patients must agree to use effective
             contraception, must be surgically sterile, or must be postmenopausal. Male patients
             must agree to use effective contraception or be surgically sterile. The definition of
             effective contraception will be based on the judgment of the principal investigator or
             a designated associate. All at-risk female patients must have a negative serum
             pregnancy test within 7 days prior to registration.

          -  Active inflammatory bowel disease, significant bowel obstruction, or chronic diarrhea
             (grade 2).

          -  Myocardial infarction or stroke within the previous 6 months, or ongoing unstable
             angina, symptomatic congestive heart failure, or serious uncontrolled cardiac
             dysrhythmia.

          -  Known human immunodeficiency virus (HIV) positivity or
             acquired-immunodeficiency-syndrome (AIDS)-related illness.

          -  No previous or concurrent malignancy is allowed except for adequately treated basal
             cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer for which
             the patient has been disease-free for 3 years.

          -  Known CNS metastases

          -  Preexisting neuropathy > Grade 2

          -  Prior therapy which specifically and directly targets the EGFR pathway

          -  Prior severe infusion reaction to a monoclonal antibody

          -  Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension,
             unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled
             congestive heart failure and cardiomyopathy with decreased ejection fraction.