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

Part of the treatment plan for this study is surgical removal of the tumor that is planned to
occur 6 to 8 weeks after completion of radiotherapy (XRT). This study consists of 2 distinct
phases (Phase 1 and Phase 2).

In Phase 1, the objectives are to

1. Assess dose-limiting toxicities (DLTs) and

2. Determine a maximum-tolerated dose (MTD)

The Phase 1 endpoints are assessed on an initial cohort of patients after the completion of
the chemo-radiotherapy regimen at defined timepoints that precede surgery.

Phase 2 is the efficacy assessment portion of this study. In Phase 2, the objective is to
accrue an expansion cohort. Efficacy assessments for phase 2 are to be assessed across all
study participants at the time of, or after, surgery, as measured by the pathologic response
rate; downstaging; and survival at 5 years from the start of treatment.

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