Tegafur-Uracil and Leucovorin or S-1 in Treating Patients With Stage III Colon Cancer That Has Been Completely Removed by Surgery

Randomized Phase III Study of UFT+Leucovorin vs. TS-1 as Adjuvant Treatment for Stage III Colon Cancer , and Investigate Predictive Factors Based on Gene Expression

RATIONALE: Drugs used in chemotherapy, such as tegafur-uracil, leucovorin, and S-1, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving tegafur-uracil together with leucovorin is more effective than giving S-1 in treating patients with stage III colon cancer.

PURPOSE: This randomized phase III trial is studying giving tegafur-uracil together with leucovorin to see how well it works compared with giving S-1 in treating patients with stage III colon cancer that has been completely removed by surgery.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: tegafur-uracil; Drug: tegafur-gimeracil-oteracil potassium; Drug: folinate calcium

Detailed Description

OBJECTIVES:

• Compare the disease-free survival of patients with stage III colon cancer treated with S-1 or tegafur-uracil and leucovorin after curative surgery .

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral tegafur-uracil and oral leucovorin 3 times daily on days 1-21. The treatment repeats 5 times every 5 weeks.
• Arm II: Patients receive oral S-1 twice daily on days 1-28. The treatment repeats 4 times every 6 weeks.

Biological samples are collected for gene expression analysis for identification of predictive markers.

• Study Type: Interventional
• Enrollment (Actual): 1535
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 113-8519
    • Tokyo Medical and Dental University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of colon

  • Stage III (T1-4, N1-3, M0) disease
• Has undergone surgical resection of the tumor within the past 8 weeks

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Able to take medications orally
• WBC ≥ 3,500/mm³ and < 12,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 2.0 mg/dL
• AST/ALT ≤ 100 IU/L
• Creatinine ≤ 1.2 mg/dL
• No other active malignancies

• Must have none of the following comorbidities:

  • Severe postoperative complications
  • Uncontrollable diabetes mellitus
  • Uncontrollable hypertension
  • Myocardial infraction within 6 months
  • Unstable angina pectoris
  • Hepatocirrhosis
  • Interstitial pneumonia, pulmonary fibrosis, or severe emphysema

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy for colon cancer
• No concurrent radiotherapy
• No concurrent biological response modifiers

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: tegafur-gimeracil-oteracil potassium; Patients receive tegafur-gimeracil-oteracil potassium(S-1) orally twice daily for 28 days with a subsequent pause of 14 days. This repeats 4 times every 6 weeks.	Drug: tegafur-gimeracil-oteracil potassium; Other Names: S-1, TS-1
Active Comparator: tegafur-uracil and folinate calcium; Patients receive tegafur-uracil(UFT) plus folinate calcium(leucovorin) orally every 8 hours for 21 days with a subsequent pause of 7 days. This repeats 5 times every 5 weeks.	Drug: tegafur-uracil; Other Names: UFT; Drug: folinate calcium; Other Names: Leucovorin, leucovorin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Disease-free survival

Secondary Outcome Measures

Outcome Measure
Overall survival
Adverse event
Pharmaco-economics
Identification of predictive markers

Collaborators and Investigators

• Sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Investigators: Principal Investigator: Kenichi Sugihara, MD, PhD, Tokyo Medical and Dental University

Publications and helpful links

General Publications

• Kusumoto T, Ishiguro M, Nakatani E, Yoshida M, Inoue T, Nakamoto Y, Shiomi A, Takagane A, Sunami E, Shinozaki H, Takii Y, Maeda A, Ojima H, Hashida H, Mukaiya M, Yokoyama T, Nakamura M, Munemoto Y, Sugihara K. Updated 5-year survival and exploratory T x N subset analyses of ACTS-CC trial: a randomised controlled trial of S-1 versus tegafur-uracil/leucovorin as adjuvant chemotherapy for stage III colon cancer. ESMO Open. 2018 Oct 7;3(6):e000428. doi: 10.1136/esmoopen-2018-000428. eCollection 2018.
• Yoshida M, Ishiguro M, Ikejiri K, Mochizuki I, Nakamoto Y, Kinugasa Y, Takagane A, Endo T, Shinozaki H, Takii Y, Mochizuki H, Kotake K, Kameoka S, Takahashi K, Watanabe T, Watanabe M, Boku N, Tomita N, Nakatani E, Sugihara K; ACTS-CC study group. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial). Ann Oncol. 2014 Sep;25(9):1743-1749. doi: 10.1093/annonc/mdu232. Epub 2014 Jun 18.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: April 16, 2008
• First Submitted That Met QC Criteria: April 16, 2008
• First Posted (Estimate): April 17, 2008

Study Record Updates

• Last Update Posted (Estimate): August 3, 2016
• Last Update Submitted That Met QC Criteria: August 2, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: adenocarcinoma of the colon; stage III colon cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Leucovorin; Calcium; Levoleucovorin; Tegafur
• Other Study ID Numbers: CDR0000593164; TMDU-TRICC0706 (Other Identifier: National Cancer Institute)