A Phase 1-2 Trial of Cetuximab in Combination With Oxaliplatin, Capecitabine, and Radiation Therapy Followed by Surgery for Locally-advanced Rectal Cancer

INCLUSION CRITERIA

   - Histologically-confirmed adenocarcinoma of the rectum. Clinical stages T3; T4; or N1
   as determined by endoscopic ultrasound; or a rectal CT or MRI scan are eligible,
   including T3 N0; T3 N1; T4 N0; T4 N1; T1-4 N1. Rectal cancers are defined as those
   whose distal border extends to within 12 cm of the anal verge.

   - Age ≥ 18

   - Karnofsky performance status (KPS) ≥ 70

   - Leukocyte count > 3,500 x 10e6/µL

   - Platelet count > 100,000/µL

   - Serum glutamic-oxaloacetic transaminase (SGOT) < 2.5 x institutional upper limits of
   normal (ULN)

   - Serum glutamic-pyruvic transaminase (SGPT) < 2.5 x ULN

   - Alkaline phosphatase < 2.5 x ULN

   - Total bilirubin < 1.5x ULN

   - Creatinine:

      - Within normal institutional limits

      - OR

      - Creatinine clearance > 60 mL/min/1.73 m2 (if serum creatinine levels above
      institutional normal)

   - Ability to swallow pills without difficulty

   - Women of child-bearing potential must have a negative serum or urine pregnancy test
   (minimum sensitivity 25 IU/L or equivalent units of HCG), within 72 hours prior to the
   start of study medication

   - Women of child-bearing potential must be using an adequate method of contraception to
   avoid pregnancy throughout the treatment

EXCLUSION CRITERIA

   - Metastatic (M1) or stage IV disease

   - Prior history of treatment with cetuximab or other therapy targeting EGFR

   - Prior history of anti-cancer murine monoclonal antibody therapy

   - Prior pelvic or whole abdominal radiotherapy

   - Uncontrolled intercurrent illness including, but not limited to:

      - Ongoing or active infection

      - Symptomatic congestive heart failure

      - Unstable angina pectoris

      - Cardiac arrhythmia

      - Psychiatric illness / social situations that would limit compliance with study
      requirements

   - Patients with a concurrent malignancy or previous malignancy within 5 years of
   screening will be excluded from this study (EXCEPTION: concurrent or previous
   non-melanoma skin cancer, hematolymphoid malignancy or carcinoma in-situ of the cervix
   may be allowed at the investigator's discretion)

   - Inability to sign written consent

   - Pregnant or breastfeeding

   - Unwilling or unable to use effective contraception in self or partner for the entire
   study period and for up to 4 weeks after the study