Comparison of Preoperative and Postoperative Radiotherapy and Capecitabine in Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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Based on the potential advantaged of preoperative chemoradiotherapy and oral fluoropyrimidine, the investigators planned a prospective randomized phase III trial which compares preoperative chemoradiotherapy and postoperative chemoradiotherapy with conventional radiation schedule and oral fluoropyrimidine to establish new standard neo-adjuvant therapy regimen in locally advanced rectal cancer.

Detailed Description
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Although there have been no confirmative data which favored preoperative chemoradiotherapy, preoperative chemoradiation have many theoretical advantage compared with postoperative one. Preoperative radiotherapy with intensive short course regimen showed significant improvement in local control even with TME, but there has been no large prospective randomized trial which proved the efficacy of preoperative chemoradiotherapy compared with the standard postoperative chemoradiotherapy. Although the final result of the German Trial may give the answer for this question, there has been no randomized controlled trial which investigated the efficacy of preoperative chemoradiotherapy using oral fluoropyrimidine which have many theoretical and clinical advantages mentioned above; the German Trial used 5-day continuous infusion of 5-FU. The investigators think that preoperative chemoradiotherapy with oral capecitabine could be new standard regimen in locally advanced rectal cancer, but this regimen must be compared with the standard postoperative chemoradiotherapy through well designed prospective randomized trial. Based on the potential advantaged of preoperative chemoradiotherapy and oral fluoropyrimidine, the investigators planned prospective randomized phase III trial which compares preoperative chemoradiotherapy and postoperative chemoradiotherapy with conventional radiation schedule and oral fluoropyrimidine to establish new standard neo-adjuvant therapy regimen in locally advanced rectal cancer.

Official Title
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Comparison of Preoperative and Postoperative Radiotherapy and Capecitabine in Locally Advanced Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Radiation: Preoperative chemoradiotherapy
* Radiation: Postoperative chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed rectal adenocarcinoma Tumor located below 10 cm from the anal verge Clinical stage T3 or potentially resectable T4, or N+ on endorectal ultrasonography (EUS) and computed tomography (CT) Patients must be > 18 years and < 76 years Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate bone marrow reserve Adequate renal function Adequate liver function Signed informed consent prior to randomization Exclusion Criteria: Evidence of distant metastasis Previous history of chemotherapy or radiotherapy History of malignancy during recent 5 years other than skin cancer Pregnant or lactating woman Familial history of colorectal cancer

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 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: Preoperative chemoradiotherapy<br>Preoperative chemoradiotherapy with conventional radiation schedule and oral fluoropyrimidine (capecitabine) | Radiation: Preoperative chemoradiotherapy<br>* Preoperative chemoradiation with conventional radiotherapy (46 Gy in 23 fractions to the whole pelvis followed by a boost dose of 4 Gy in 2 fractions) and oral fluoropyrimidine (capecitabine 825 mg/m2 twice per day without weekend breaks during whole radiotherapy period)<br>* Other names: Preoperative CCRT;|
| Active Comparator: Postoperative chemoradiotherapy<br>Postoperative chemoradiotherapy with conventional radiation schedule and oral fluoropyrimidine (capecitabine) | Radiation: Postoperative chemoradiotherapy<br>* Postoperative radiotherapy with conventional radiation schedule (50 Gy in 25 fractions to the whole pelvis) and oral fluoropyrimidine (capecitabine 825 mg/m2 twice per day without weekend breaks during whole radiotherapy period)<br>* Other names: Postoperative CCRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival |  | Three year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Three year | 
| Local relapse-free survival |  | Three year | 
| Sphincter preservation rate |  | Three year | 
| Treatment related toxicities |  | Three year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal cancer, Preoperative CCRT, Postoperative CCRT, Capecitabine