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

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Oxaliplatin may make tumor cells more sensitive to radiation therapy. Giving capecitabine and oxaliplatin together with radiation therapy before surgery may shrink the tumor so it can be removed. PURPOSE: This phase II trial is studying how well giving capecitabine and oxaliplatin together with radiation therapy works in treating patients who are undergoing surgery for stage I rectal cancer.

Detailed Description
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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.

Official Title
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A Phase II Trial of Chemoradiotherapy and Local Excision for uT2uN0 Rectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: oxaliplatin
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (capecitabine, oxaliplatin, radiotherapy, surgery)<br>Patients undergo high-dose external beam radiotherapy once daily and receive capecitabine PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive 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. | Drug: capecitabine<br> <br> * Other names: Given IV;Drug: oxaliplatin<br>* Given IV<br>Procedure: neoadjuvant therapy<br>* Undergo surgery<br>* Other names: therapeutic conventional surgery;Radiation: radiation therapy<br>* Undergo radiotherapy<br>* Other names: irradiation, radiotherapy, therapy, radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-Year Disease-free Survival | The primary endpoint was 3-year disease-free survival (DFS). Evidence of local recurrence, distant metastasis, or death from any cause within 3 years counted as events in the time-to-event Kaplan-Meier analysis of disease-free survival. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 Resection Rate (Negative Margin Rate) | The rate (percentage) of patients with negative resection margins after undergoing local excision is reported below. | At time of surgery | 
| Morbidity and Mortality Rate | Morbidity and mortality after neoadjuvant cheoradiotherapy and local excision. | Up to 30 days | 
| Rate of Pathologic Complete Response of the Primary Tumor | The rate (percentage) of patients with pathologic complete response (pCR) is reported below. Pathologic response will be determined by comparing tumor width and stage in the surgical specimen with the same parameters as determined by pre-CRT ERUS: PATHOLOGIC COMPLETE RESPONSE (pCR): no residual tumor. | Up to 5 years | 
| Local Recurrence Rate | The local recurrence rate (percentage) is defined as the percentage of patients who had local recurrence as initial sites of failure at the end of follow-up. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the rectum, stage I rectal cancer