Intensity-Modulated Radiation Therapy With Incorporated Boost and Capecitabine Before Surgery in Treating Patients With Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Intensity-modulated radiation therapy (radiation directed at the tumor more precisely than in standard radiation therapy) with incorporated boost (an increase in the amount of radiation given during treatment) may cause less damage to normal tissue. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy together with chemotherapy before surgery may shrink the tumor so it can be removed. PURPOSE: This phase I trial is studying the side effects and best dose of neoadjuvant intensity-modulated radiation therapy with incorporated boost when given together with capecitabine in treating patients with locally advanced rectal cancer.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of neoadjuvant boost intensity-modulated radiotherapy when combined with capecitabine before surgery in patients with locally advanced rectal cancer. Secondary Determine the pathologic tumor response in patients treated with this regimen. Determine the quality of life of patients treated with this regimen. OUTLINE: This is a dose-escalation study of boost intensity-modulated radiotherapy (IMRT). Patients undergo neoadjuvant IMRT with incorporated boost once daily 5 days a week for 5 weeks. Beginning on the first day of radiotherapy, patients receive oral capecitabine twice daily 7 days a week for 5 weeks. Patients undergo surgical resection 4-8 weeks after completion of chemoradiotherapy. Cohorts of 3-6 patients undergo escalating doses of boost IMRT until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. Quality of life is assessed at baseline, at week 5 of chemoradiotherapy, before surgery, and then at 1, 3, and 12 months after surgery. Patients are followed at 1, 3, and 12 months after surgery. PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for this study.

Official Title
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Phase I Study of Preoperative Intensity Modulated Radiation Therapy (IMRT) With Incorporated Boost and Oral Capecitabine in Locally Advanced Rectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: capecitabine
* 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 primary adenocarcinoma of the rectum Distal border of the tumor within 12 cm of the anal verge by proctoscopic exam Clinical stage T3-4, N1-2 (stage II or III) disease by 2 of the following tests: Physical exam Transrectal ultrasound Pelvic CT scan Pelvic MRI No clinical evidence of metastatic disease PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy More than 3 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No known, uncontrolled coagulopathy Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) SGOT and SGPT ≤ 1.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Renal Creatinine ≤ 1.5 times normal Creatinine clearance > 50 mL/min Cardiovascular No clinically significant cardiac disease No congestive heart failure No symptomatic coronary artery disease No poorly controlled cardiac arrhythmias No myocardial infarction within the past year Gastrointestinal No active inflammatory bowel disease No lack of physical integrity of the upper gastrointestinal tract No malabsorption syndrome Other No other prior or concurrent malignancy except inactive, non-invasive carcinoma of the cervix or non-melanoma skin cancer No concurrent serious, uncontrolled infection(s) No prior unanticipated severe reaction to fluoropyrimidine therapy No known sensitivity to fluorouracil No prior uncontrolled seizures No CNS disorders that would preclude study participation No other medical or psychiatric condition that would preclude study participation Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy No prior immunotherapy for rectal cancer Chemotherapy No prior chemotherapy for rectal cancer Endocrine therapy Not specified Radiotherapy No prior radiotherapy for rectal cancer No prior pelvic radiotherapy Surgery More than 4 weeks since prior major surgery and recovered No prior surgery for rectal cancer Other More than 4 weeks since prior participation in another investigational drug study No concurrent celecoxib

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: capecitabine|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute toxicity by CTCAE at 6 weeks following study completion |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life as assessed by Quality of Life Questionnaire Core 30 Items (QLQ-C30) before and after radiotherapy and then every 6 months after surgery |  |  | 

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