Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Stage I Rectal Cancer

OBJECTIVES:

Primary

- Determine the 3-year disease-free survival rate in patients with stage I adenocarcinoma
of the rectum treated with neoadjuvant chemoradiotherapy comprising capecitabine,
oxaliplatin, and radiotherapy followed by local excision.

Secondary

- Determine the rate of resectability with negative resection margins in patients treated
with this regimen.

- Determine the procedure-specific morbidity and mortality in patients treated with this
regimen.

- Determine the rate of pathologic complete response of the primary tumor in patients
treated with this regimen.

- Determine the impact of this regimen on anorectal function and quality of life in these
patients.

- Determine the feasibility of using molecular studies to assess surgical resection
margins and tumor response in patients treated with this regimen.

- Determine molecular markers associated with local tumor recurrence in patients treated
with this regimen.

OUTLINE: This is a non-randomized, multicenter study.

Patients undergo high-dose external beam radiotherapy once daily on days 1-5, 8-12, 15-19,
22-26, and 29-33. Patients also receive oral capecitabine twice daily on days 1-14 and 22-35
and oxaliplatin IV over 2 hours on days 1, 8, 22, and 29. Approximately 4-8 weeks after
completion of chemoradiotherapy, patients undergo local excision of the tumor. Patients with
T3 disease or positive resection margins after local excision undergo radical resection of
the rectum and receive additional chemotherapy and/or radiotherapy at the discretion of the
physician.

Quality of life is assessed at baseline and then 1 year after surgery.

After completion of study treatment, patients are followed at 1 month, every 4 months for 3
years, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 102 patients will be accrued for this study within 2.8 years.

- Patient must have an Eastern Cooperative Oncology Group (ECOG)/Zubrod status of =< 2

- Patient must have histologically confirmed invasive adenocarcinoma of the rectum;
Note: patients with rectal tumors suspicious for invasion also are eligible

- Distal border of the patient's tumor must be within 8 cm from the anal verge as
measured on endoscopic exam

- Patients with tumors fixed to adjacent structures on digital exam are NOT eligible

- Patient must have an uT2uN0 tumor, as confirmed by endorectal ultrasound (ERUS) or
endorectal coil magnetic resonance imaging (MRI) scan; patients with uT1, uT3, or uT4
tumors are NOT eligible; greatest diameter of tumor cannot exceed 4 cm

- Patients with positive perirectal nodes on ERUS examination are NOT eligible

- Patients with histologic evidence of metastatic invasion of inguinal lymph nodes are
NOT eligible

- Patients with the following conditions are NOT allowed on study:

- Metastatic disease or other primaries (patient must have had chest X-ray/computed
tomography [CT] and abdominal & pelvic CT/MRI with IV contrast, as well as a
colonoscopy)

- Previously documented history of familial adenomatous polyposis

- Previously documented history of hereditary non-polyposis colorectal cancer
diagnosed clinically (Amsterdam II criteria) or by genetic testing

- History of inflammatory bowel disease

- History of prior radiation treatments to pelvis

- Clinically significant peripheral sensory or motor neuropathy (defined as
symptomatic weakness, paresthesia or sensory alteration described to be
interfering with function, interfering with activities of daily living, disabling
or life-threatening)

- History of any clinically significant cardiac disease (i.e., class 3-4 congestive
heart failure, symptomatic coronary artery disease, uncontrolled arrhythmia,
and/or myocardial infarction within the last 6 months)

- History of uncontrolled seizures or clinically significant central nervous system
disorders

- History of psychiatric conditions or diminished mental capacity that could
compromise the giving of informed consent, or interfere with study compliance

- History of allergy and/or hypersensitivity to capecitabine and/or oxaliplatin

- History of difficulty or inability to take or absorb oral medications

- White blood cells (WBC) >= 3000/mm^3

- Absolute neutrophil count (ANC) > 1,500/mm^3

- Hemoglobin > 9.5 mg/dl

- Platelet count >= 100,000/mm^3

- Total bilirubin =< 3 mg/dl

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0
times institutional upper limit of normal (ULN)

- Alkaline phosphatase =< 2.0 times ULN

- Creatinine clearance (CLcr) >= 50 ml/min by Cockroft-Gault equation

- Patients who have experienced a prior malignancy must have received potentially
curative therapy for that malignancy, and must be cancer-free for at least five years
from the date of initial diagnosis (exceptions: patients treated for non-melanoma skin
carcinoma, or in-situ carcinomas)

- Patients of reproductive potential must agree to use an effective method of birth
control when undergoing treatments with known or possible mutagenic or teratogenic
effects; all female participants of childbearing potential must have a negative urine
or serum pregnancy test within two weeks prior to study registration