Adjuvant Chemotherapy After Preoperative Chemoradiotherapy to Treat Rectal Cancer

Phase 2

Completed

• Conditions: Rectal Cancer
• Interventions: Drug: Adjuvant FL; Drug: Adjuvant FOLFOX

• Registration Number: NCT00807911
• Lead Sponsor: Asan Medical Center

Brief Summary

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.

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 Timeline

• Study Start: 2008-11-01
• Study First Submitted: 2008-12-11
• Study First Submitted QC: 2008-12-11
• Study First Posted: 2008-12-12
• Primary Completion: 2013-06-30
• Study Completion: 2014-09-05
• Results First Submitted: 2021-02-14
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-21
• Last Update Submitted: 2024-10-21
• Results First Posted: 2024-10-23
• Last Update Posted: 2024-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 322

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Adjuvant FL	Adjuvant FL	FL (5-FU 380 mg/m2, leucovorin 20 mg/m2 on D1-5 q 4 weeks X 4 cycles)
Adjuvant FOLFOX	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)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Disease Recurrence	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
Number of Participants With Disease Recurrence With Pathological Stage III	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.
Number of Participants With Disease Recurrence With Pathological Stage II	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.

Secondary Outcome Measures

Name	Time	Method
Death Rate	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.
Pattern of Recurrence	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.

Trial Locations

Locations (6)

Seoul National Unversity Bundang Hospital; 🇰🇷 Seongnam, Korea, Republic of

National Cancer Center; 🇰🇷 Goyang, Korea, Republic of

Yeonsei University Hosptial; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of