A Study of Xeloda (Capecitabine) Compared With 5-Fluorouracil in Combination With Low-Dose Leucovorin in Patients Who Have Undergone Surgery for Colon Cancer

An Open-Label Randomized Phase III Study Comparing Xeloda (Capecitabine) With IV Bolus 5-Fluorouracil in Combination With Low-Dose Leucovorin as Adjuvant Chemotherapy in Patients Who Underwent Surgery for Dukes C Colon Cancer

This 2 arm study will compare the safety and efficacy of oral Xeloda, or 5-fluorouracil in combination with leucovorin, in patients who have undergone surgery for colon cancer. Patients will be randomized to receive either Xeloda 1250mg/m2 po bid on days 1-14 every 21 days, or leucovorin 20mg/m2 iv + 5-fluorouracil 425mg/m2 iv daily from day 1 to day 5 every 28 days. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Capecitabine [Xeloda]; Drug: 5-Fluorouracil; Drug: Leucovorin

• Study Type: Interventional
• Enrollment (Actual): 1987
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
  • Buenos Aires, Argentina, C1270AAE
  • Buenos Aires, Argentina, C1264AAA
  • Buenos Aires, Argentina, 1417
• Australia
  • Adelaide, Australia, 5011
  • Bendigo, Australia, 3550
  • Brisbane, Australia, 4006
  • Fitzroy, Australia, 3065
  • Kurralta Park, Australia, 5037
  • Melbourne, Australia, 3128
  • Melbourne, Australia, 3181
  • Perth, Australia, 6000
  • Port Macquarie, Australia, 2444
  • St. Leonards, Australia, 2065
  • Sydney, Australia, 2217
  • Wodonga, Australia, 3690
• Austria
  • Hall in Tirol, Austria, 6060
  • Innsbruck, Austria, 6020
  • Klagenfurt, Austria, 9026
  • Linz, Austria, 4010
  • Oberwart, Austria, 7400
  • St Pölten, Austria, 3100
  • Wien, Austria, 1030
  • Wien, Austria, 1100
  • Wien, Austria, 1160
  • Wien, Austria, 1220
  • Wien, Austria, 1090
• Belgium
  • Bruxelles, Belgium, 1090
• Brazil
  • Porto Alegre, Brazil, 90020-090
  • Rio de Janeiro, Brazil, 20220-410
  • Sao Paulo, Brazil, 01406100
  • Sorocaba, Brazil, 18035-300
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
• Germany
  • Berlin, Germany, 13353
  • Braunschweig, Germany, 38100
  • Freiburg, Germany, 79106
  • Grenzach-wyhlen, Germany, 79639
  • Göttingen, Germany, 37073
  • Halle, Germany, 06108
  • Hannover, Germany, 30171
  • Kassel, Germany, 34125
  • Lehrte, Germany, 31275
  • Magdeburg, Germany, 39130
  • München, Germany, 81245
  • Oldenburg, Germany, 26121
  • Oldenburg, Germany, 26133
  • Ravensburg, Germany, 88212
  • Regensburg, Germany, 93053
  • Villingen-schwenningen, Germany, 78052
  • Wuppertal, Germany, 42210
• Israel
  • Haifa, Israel, 34354
  • Petach Tikva, Israel, 49100
  • Petach Tikva, Israel
  • Rehovot, Israel, 76100
  • Tel Aviv, Israel, 6423906
• Italy
  • Aviano, Italy, 33081
  • Bergamo, Italy, 24128
  • Bologna, Italy, 40138
  • Cuneo, Italy, 12100
  • Genova, Italy, 16132
  • Livorno, Italy, 57100
  • Mantova, Italy, 46100
  • Milano, Italy, 20121
  • Mirano, Italy, 30035
  • Modena, Italy, 41100
  • Napoli, Italy, 80131
  • Pisa, Italy, 56100
  • Roma, Italy, 00135
  • Roma, Italy, 00168
  • Roma, Italy
  • Terni, Italy, 05100
  • Torino, Italy, 10126
  • Torino, Italy, 10123
  • Vecchiazzano, Italy, 47100
  • Venezia, Italy, 30122
  • Vicenza, Italy, 36100
• Portugal
  • Lisboa, Portugal, 1649-035
  • Porto, Portugal, 4200-072
• Spain
  • Bilbao, Spain, 48013
  • Cordoba, Spain, 14004
  • El Palmar Murcia, Spain, 30120
  • Elche, Spain, 03203
  • Jaen, Spain, 23007
  • Madrid, Spain, 28006
  • Madrid, Spain, 28040
  • Madrid, Spain, 28007
  • Madrid, Spain, 28222
  • Navarra, Spain, 31008
  • Palma de Mallorca, Spain, 07014
  • Valencia, Spain, 46010
• Switzerland
  • Basel, Switzerland, 4031
  • Basel, Switzerland, 4070
  • Bellinzona, Switzerland, 6500
  • Bern, Switzerland, 3010
  • St Gallen, Switzerland, 9006
  • Zürich, Switzerland, 8091
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
  • Belfast, United Kingdom, BT9 7AB
  • Cardiff, United Kingdom, CF14 2TL
  • Edinburgh, United Kingdom, EH4 2XU
  • Glasgow, United Kingdom, G12 0YN
  • Glasgow, United Kingdom, G4 OSF
  • Guildford, United Kingdom, GU2 7XX
  • Leicester, United Kingdom, LE1 5WW
  • Luton, United Kingdom, LU4 0DZ
  • Manchester, United Kingdom, M20 4BX
  • Newcastle Upon Tyne, United Kingdom, NE4 6BE
  • Northwood, United Kingdom, HA6 2RN
  • Plymouth, United Kingdom, PL6 8DH
  • Salisbury, United Kingdom, SP2 8BJ
  • Southampton, United Kingdom, SO9 4PE
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
  • Arizona
    • Phoenix, Arizona, United States, 85012
  • California
    • Fountain Valley, California, United States, 92708
    • Los Angeles, California, United States, 90089
  • Connecticut
    • Hartford, Connecticut, United States, 06102-5037
  • Florida
    • Miami, Florida, United States, 33176
  • Georgia
    • Decatur, Georgia, United States, 30033
  • Missouri
    • Columbia, Missouri, United States, 65203
    • St Louis, Missouri, United States, 63141
  • New York
    • Albany, New York, United States, 12208
    • Buffalo, New York, United States, 14263
  • Ohio
    • Cleveland, Ohio, United States, 44195
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1632
  • Texas
    • Austin, Texas, United States, 78705
    • Tyler, Texas, United States, 75701
  • Washington
    • Seattle, Washington, United States, 98195

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients 18-75 years of age;
• histologically confirmed colon cancer with potentially curative resection of the tumor within 8 weeks before study initiation.

Exclusion Criteria:

• previous chemotherapy

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: Capecitabine; Participants received capecitabine 1250 milligram per square meter (mg/m ^ 2) orally, twice a day, for 14 days, followed by a 7-day rest period without treatment, as an intermittent therapy in a 3-week cycle for 8 cycles (24 weeks).	Drug: Capecitabine [Xeloda]; 1250mg/m2 po bid on days 1-14 every 21 days.
Active Comparator: 5-Fluorouracil + Leucovorin; Participants received leucovorin 20 mg/m ^ 2 followed by 5-fluorouracil at 425 mg/m ^ 2, by rapid intravenous injection, daily, from Days 1 to 5 of the first week in each 4-week cycle for 6 cycles (24 weeks).	Drug: 5-Fluorouracil; 425mg/m2 iv daily from day 1 to day 5 every 28 days.; Drug: Leucovorin; 20mg/m2 iv daily from day 1 to day 5 every 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival	Participants with disease-free survival were reported. Disease-free survival was assessed as the number of days between randomization and the first time at which relapse, a new occurrence of colon cancer, or death was recorded, or the last time at which a participant was known to be disease free (censoring time).	Approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-Free Survival	Participants with relapse-free survival were reported. Relapse-free survival was assessed as the number of days between randomization and the first time at which relapse, a new occurrence of colon cancer, or death was recorded, or the last time at which a participants was known to be disease free (censoring time), excluding deaths that were not related to treatment or to disease progression.	Approximately 3 years
Overall Survival	Participants with overall survival were reported. Overall survival was assessed as the number of days between randomization and death or the last time at which a participant was known to be alive (censoring time).	Approximately 3 years
Mean Change From Baseline in Global Health Status at Week 25	Global health status was assessed as a sub scale of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. It was scored on a scale of 0-100; where higher score indicates better quality of life. Wherever the scores for the participants were not available, the last value carried forward (LVCF) were used.	Baseline (Days -7 to 1) and at Week 25
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters	Laboratory abnormalities were categorized according to the National Cancer Institute of Canada Common Toxicity Criteria (NCIC - CTC) grading system (May 1991 revised) as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life- threatening). Participants with abnormalities in hemoglobin, granulocytes, lymphocytes, neutrophils, neutrophils/granulocytes, platelets, white blood cell, potassium, serum creatinine, sodium, total bilirubin, alanine transaminase, aspartate aminotransferase, alkaline phosphatase, calcium (hyper), and calcium (hypo) with Grades 1-4 were presented.	Up to Week 25
Number of Participants With Any Adverse Events and Serious Adverse Events	An Adverse Event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An Serious Adverse Events (SAEs) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.	Up to Week 29

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: November 1, 1998
• Primary Completion (Actual): April 1, 2004
• Study Completion (Actual): April 1, 2004

Study Registration Dates

• First Submitted: February 2, 2001
• First Submitted That Met QC Criteria: March 16, 2004
• First Posted (Estimate): March 17, 2004

Study Record Updates

• Last Update Posted (Estimate): June 22, 2016
• Last Update Submitted That Met QC Criteria: May 16, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• 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; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Capecitabine; Leucovorin
• Other Study ID Numbers: M66001