Radiation Therapy and Capecitabine With or Without Oxaliplatin in Treating Patients Who Are Undergoing Surgery for Stage II or Stage III Rectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving radiation therapy together with combination chemotherapy before surgery may shrink the tumor so it can be removed. It is not yet known whether giving radiation therapy together with capecitabine is more effective with or without oxaliplatin before surgery in treating rectal cancer. PURPOSE: This randomized phase III trial is studying radiation therapy, capecitabine, and oxaliplatin to see how well they work compared to radiation therapy and capecitabine in treating patients who are undergoing surgery for stage II or stage III rectal cancer.

Detailed Description
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OBJECTIVES: Primary Compare the efficacy of neoadjuvant chemoradiotherapy comprising radiotherapy and capecitabine with vs without oxaliplatin followed by total mesorectal excision, in terms of the rate of complete surgical resection, in patients with resectable stage II or III rectal cancer. Secondary Compare overall and disease-free survival of patients treated with these regimens. Compare clinical tumor response in patients treated with these regimens. Compare acute and late toxicity of these regimens in these patients. Determine biological parameters that predict tumor response and treatment-related toxicity in patients treated with these regimens. Compare sphincter preservation and function in patients treated with these regimens. OUTLINE: This is a randomized, controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo radiotherapy once daily 5 days a week and receive capecitabine once daily 5 days a week in weeks 1-5. Arm II: Patient undergo radiotherapy and receive capecitabine as in arm I. Patients also receive oxaliplatin once weekly in weeks 1-5. All patients undergo total mesorectal excision 6 weeks after completion of chemoradiotherapy. PROJECTED ACCRUAL: A total of 590 patients will be accrued for this study.

Official Title
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Randomized Phase III Trial Comparing in a Preoperative Schedule the Result of Two Concurrent Chemoradiation Schemes (45 Gy + Capecitabine vs 50 Gy + Capecitabine - Oxaliplatin) on the Rate of Sterilization of the Operative Specimen in Resectable Rectal Carcinomas T3-4 No-2 Mo

Conditions
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Colorectal Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the rectum T3-4, N0-2, M0 disease by endorectal ultrasound T2 disease located in the low rectum allowed provided lower pole is ≤ 6 cm from the anal verge Tumor must be accessible to digital rectal examination (i.e., tumor located at low- or mid-rectum) Resectable disease treatable with chemoradiotherapy No unresectable disease (i.e., T4 disease with high risk for incomplete gross resection [i.e., R2]) PATIENT CHARACTERISTICS: Age 18 to 80 Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic WBC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin > 10 g/dL Hepatic Alkaline phosphatase normal Bilirubin normal Renal Creatinine ≤ 130 μmol/L No severe renal insufficiency Cardiovascular No cardiac insufficiency No symptomatic coronary artery disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No contraindication to study treatment Prior acute intestinal obstruction allowed provided patient underwent surgical diversion with stoma No history of other cancer except basal cell skin cancer or carcinoma in situ of the cervix No peripheral neuropathy No uncontrolled diabetes No other uncontrolled severe disease No geographical, social, or psychological condition that would preclude study follow-up PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for cancer No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy for cancer Surgery Not specified Other No concurrent phenytoin No concurrent participation in another clinical trial of an experimental medical treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiothérapie + Xelox<br> | Drug: capecitabine<br> <br> Drug: oxaliplatin<br> <br> Procedure: conventional surgery<br> <br> Procedure: neoadjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |
| Active Comparator: Radiothérapie + Capécitabine<br> | Drug: capecitabine<br> <br> Procedure: conventional surgery<br> <br> Procedure: neoadjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete surgical resection |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 
| Disease-free survival |  |  | 
| Sphincter preservation |  |  | 
| Sphincter function |  |  | 
| Biological parameters that predict tumor response and treatment-related toxicity |  |  | 
| Acute and late toxicity |  |  | 

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