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

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.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer
• Intervention / Treatment: Radiation: Preoperative chemoradiotherapy; Radiation: Postoperative chemoradiotherapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preoperative chemoradiotherapy; Preoperative chemoradiotherapy with conventional radiation schedule and oral fluoropyrimidine (capecitabine)	Radiation: Preoperative chemoradiotherapy; 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); Other Names: Preoperative CCRT
Active Comparator: Postoperative chemoradiotherapy; Postoperative chemoradiotherapy with conventional radiation schedule and oral fluoropyrimidine (capecitabine)	Radiation: Postoperative chemoradiotherapy; 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); Other Names: Postoperative CCRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease-free survival	Three year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Jong Hoon Kim, M.D., Ph.D., Asan Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: August 18, 2010
• First Submitted That Met QC Criteria: August 20, 2010
• First Posted (Estimate): August 23, 2010

Study Record Updates

• Last Update Posted (Estimate): August 23, 2010
• Last Update Submitted That Met QC Criteria: August 20, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Capecitabine; Rectal cancer; Preoperative CCRT; Postoperative CCRT
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: AMC Rectal Pre Vs Post 2004