Adjuvant Chemotherapy After Preoperative Chemoradiotherapy to Treat Rectal Cancer

October 21, 2024 updated by: Tae Won Kim, Asan Medical Center

Randomized Phase II Study of Adjuvant Chemotherapy With 5-FU/Leucovorin vs. Oxaliplatin/5-FU/Leucovorin After Preoperative Chemoradiotherapy With Fluoropyrimidines Followed by Surgery in Patients With Locally Advanced Rectal Cancer

The purpose of this study is to evaluate the disease-free survival in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy with fluoropyrimidines and surgery followed by adjuvant combination chemotherapy with oxaliplatin/5-FU/Leucovorin vs 5-FU/Leucovorin.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Preoperative chemoradiotherapy with fluoropyrimidines followed by surgery is one of the standard treatments for patients with locally advanced rectal cancer; however, the role of adjuvant chemotherapy is still controversial. The aim of this study is to investigate the efficacy of adjuvant FOLFOX for rectal cancer who underwent fluoropyrimidine based chemoradiotherapy and complete total mesorectal excision.

Study Type

Interventional

Enrollment (Actual)

322

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Goyang, Korea, Republic of
        • National Cancer Center
      • Seongnam, Korea, Republic of
        • Seoul National Unversity Bundang Hospital
      • Seoul, Korea, Republic of
        • Seoul National University Hospital
      • Seoul, Korea, Republic of
        • Asan Medical Center
      • Seoul, Korea, Republic of
        • Samsung Medical Center
      • Seoul, Korea, Republic of
        • Yeonsei University Hosptial

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically confirmed adenocarcinoma of the rectum
  2. Patients who treated with preoperative chemoradiation with fluoropyrimidines followed by curative surgery without microscopic residual tumor.
  3. AJCC/UICC pathologic stages of ypT3-4 or ypN+
  4. Curative surgery not less than 3 and not more than 8 weeks prior to randomization
  5. No prior chemotherapy, radiotherapy and immunotherapy except preoperative chemoradiation for rectal cancer
  6. ECOG PS 0-1
  7. Adequate organ function
  8. Informed Consent

Exclusion Criteria:

  1. Macroscopic or microscopic evidence of remaining tumor
  2. Any histologic feature other than adenocarcinoma or arisen from chronic inflammatory bowel disease
  3. More than 8 weeks after curative surgery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Adjuvant FL
FL (5-FU 380 mg/m2, leucovorin 20 mg/m2 on D1-5 q 4 weeks X 4 cycles)
Drug: Adjuvant FL
5-Fluorouracil 380 mg/m2, leucovorin 20 mg/m2 on D1-5 q 4 weeks X 4 cycles
Other Names:
  • fluorouracil, leucovorin
Experimental: Adjuvant FOLFOX
FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 on D1, 5-FU bolus 400 mg/m2 on D1, 5-FU infusion 2400 mg/m2 for 46 hours q 2 weeks X 8 cycles)
Drug: Adjuvant FOLFOX
oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 on D1, 5-Fluorouracil bolus 400 mg/m2 on D1, 5-Fluorouracil continuous infusion 2400 mg/m2 for 46 hours q 2 weeks X 8 cycles
Other Names:
  • fluorouracil, oxaliplatin, leucovorin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Disease Recurrence
Time Frame: up to 3 years after completion of treatment
Disease-free survival will be measured as the time from the date of randomization to the date of disease relapse or death due to any cause. Using Cox-proportional hazard regression, the hazard ratio together with the 95% confidence interval will be reported, in addition to Kaplan-Meier estimates of the survival curves, including medians and rates with 95% confidence intervals. Intent-to-treat population included all randomised patients, and per-protocol population included patients who received at least 1 dose of chemotherapy without any violation of inclusion criteria
up to 3 years after completion of treatment
Number of Participants With Disease Recurrence With Pathological Stage III
Time Frame: up to 3 years after completion of treatment
Disease-free survival will be measured as the time from the date of randomization to the date of disease relapse or death due to any cause. Using Cox-proportional hazard regression, the hazard ratio together with the 95% confidence interval will be reported, in addition to Kaplan-Meier estimates of the survival curves, including medians and rates with 95% confidence intervals. Intent-to-treat population included all randomised patients, and per-protocol population included patients who received at least 1 dose of chemotherapy without any violation of inclusion criteria.
up to 3 years after completion of treatment
Number of Participants With Disease Recurrence With Pathological Stage II
Time Frame: up to 3 years after completion of treatment
Disease-free survival will be measured as the time from the date of randomization to the date of disease relapse or death due to any cause. Using Cox-proportional hazard regression, the hazard ratio together with the 95% confidence interval will be reported, in addition to Kaplan-Meier estimates of the survival curves, including medians and rates with 95% confidence intervals. Intent-to-treat population included all randomised patients, and per-protocol population included patients who received at least 1 dose of chemotherapy without any violation of inclusion criteria.
up to 3 years after completion of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death Rate
Time Frame: Up to 3 years after completion of treatment.
overall survival was defined as the time from randomisation to death. We used the Kaplan-Meier method to estimate disease-free and overall survival. Patients were censored at the last follow-up if they were alive and free from disease recurrence. We used the log-rank test to compare the two survival distributions. We estimated crude and stratified hazard ratios (HRs) and their corresponding 95% CIs using the Cox proportionalhazards regression model.
Up to 3 years after completion of treatment.
Pattern of Recurrence
Time Frame: the time from the date of randomization to the date of disease relapse, , assessed up to 5 years
After the completion of study treatment, chest radiography and measurement of carcinoembryonic antigen were done every 3 months for the fi rst 2 years and every 6 months thereafter. Abdominopelvic CT scans were done every 6 months and chest CT scans annually. Colonoscopy was scheduled at 1 year, 3 years, and 5 years from the date of surgery. Local recurrence was defined as any clinically proven tumour relapse within the pelvis or perineum. Distant metastasis was defined as relapse at any other site rather than local recurrence. We regarded any local or distant recurrence as a disease recurrence event. Disease recurrence was judged by the investigators with no central review.
the time from the date of randomization to the date of disease relapse, , assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Investigators

  • Principal Investigator: Tae Won Kim, Professor, Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2008

Primary Completion (Actual)

June 30, 2013

Study Completion (Actual)

September 5, 2014

Study Registration Dates

First Submitted

December 11, 2008

First Submitted That Met QC Criteria

December 11, 2008

First Posted (Estimated)

December 12, 2008

Study Record Updates

Last Update Posted (Actual)

October 23, 2024

Last Update Submitted That Met QC Criteria

October 21, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMC-0256

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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