Trial Outcomes & Findings for A Study of Xeloda (Capecitabine) Compared With 5-Fluorouracil in Combination With Low-Dose Leucovorin in Patients Who Have Undergone Surgery for Colon Cancer (NCT NCT00009737)

Last Updated: 2016-06-22

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1987 participants

Primary outcome timeframe

Approximately 3 years

Results posted on

2016-06-22

Participant Flow

A total of 1987 participants were recruited into the study across 164 centers in 25 countries. This study was conducted from 12 Nov 1998 to 01 Apr 2004.

Participant milestones

Participant milestones
Measure	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).	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).
Overall Study STARTED	1004	983
Overall Study COMPLETED	834	860
Overall Study NOT COMPLETED	170	123

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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).
Overall Study Adverse Event	112	75
Overall Study Death	4	6
Overall Study Lack of Efficacy	17	15
Overall Study Violation of Selection Criteria at Entry	13	9
Overall Study Other Protocol Violation	1	0
Overall Study Refused Treatment	15	16
Overall Study Lost to Follow-up	1	1
Overall Study Administrative/Other Reasons	7	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Capecitabine n=1004 Participants Participants received capecitabine 1250 (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).	5-Fluorouracil + Leucovorin n=983 Participants 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).	Total n=1987 Participants Total of all reporting groups
Age, Continuous	62.0 Years n=5 Participants	63.0 Years n=7 Participants	62.0 Years n=5 Participants
Sex/Gender, Customized Female	461 Participants n=5 Participants	451 Participants n=7 Participants	912 Participants n=5 Participants
Sex/Gender, Customized Male	542 Participants n=5 Participants	532 Participants n=7 Participants	1074 Participants n=5 Participants
Sex/Gender, Customized Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 3 years

Population: All randomized population included all participants who were randomized to one of the two treatment arms, regardless of whether they received any study medication.

Outcome measures

Outcome measures
Measure	Capecitabine n=1004 Participants Participants received capecitabine 1250 (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).	5-Fluorouracil + Leucovorin n=983 Participants 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).
Disease-free Survival	656 Participants	603 Participants

SECONDARY outcome

Timeframe: Approximately 3 years

Population: All randomized population included all participants who were randomized to one of the two treatment arms, regardless of whether they received any study medication.

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.

Outcome measures

Outcome measures
Measure	Capecitabine n=1004 Participants Participants received capecitabine 1250 (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).	5-Fluorouracil + Leucovorin n=983 Participants 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).
Relapse-Free Survival	677 Participants	621 Participants

SECONDARY outcome

Timeframe: Approximately 3 years

Population: All randomized population included all participants who were randomized to one of the two treatment arms, regardless of whether they received any study medication.

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).

Outcome measures

Outcome measures
Measure	Capecitabine n=1004 Participants Participants received capecitabine 1250 (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).	5-Fluorouracil + Leucovorin n=983 Participants 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).
Overall Survival	804 Participants	756 Participants

SECONDARY outcome

Timeframe: Baseline (Days -7 to 1) and at Week 25

Population: The safety population included all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment (adverse events, laboratory test results, or vital signs).

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.

Outcome measures

Outcome measures
Measure	Capecitabine n=836 Participants Participants received capecitabine 1250 (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).	5-Fluorouracil + Leucovorin n=769 Participants 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).
Mean Change From Baseline in Global Health Status at Week 25	2.1 Score on a scale Standard Error 0.80	2.6 Score on a scale Standard Error 0.78

SECONDARY outcome

Timeframe: Up to Week 25

Population: The safety population comprises all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.

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.

Outcome measures

Outcome measures
Measure	Capecitabine n=995 Participants Participants received capecitabine 1250 (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).	5-Fluorouracil + Leucovorin n=974 Participants 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).
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Alanine transaminase	327 Participants	333 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Aspartate aminotransferase	300 Participants	288 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Alkaline Phosphatase	334 Participants	289 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Calcium (Hyper)	67 Participants	68 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Calcium (Hypo)	150 Participants	112 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Granulocytes	20 Participants	43 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Hemoglobin	691 Participants	650 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Lymphocytes	778 Participants	744 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Neutrophils	308 Participants	596 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Neutrophils/Granulocytes	316 Participants	612 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Platelets	182 Participants	160 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Potassium	209 Participants	156 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Serum Creatinine	157 Participants	138 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Sodium	189 Participants	184 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters Total Bilirubin	501 Participants	185 Participants
Number of Participants With Abnormalities for Blood Chemistry and Hematological Parameters White blood cell	220 Participants	409 Participants

SECONDARY outcome

Timeframe: Up to Week 29

Population: The safety population comprises all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment

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.

Outcome measures

Outcome measures
Measure	Capecitabine n=995 Participants Participants received capecitabine 1250 (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).	5-Fluorouracil + Leucovorin n=974 Participants 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).
Number of Participants With Any Adverse Events and Serious Adverse Events All adverse events	910 Participants	885 Participants
Number of Participants With Any Adverse Events and Serious Adverse Events Serious adverse events	181 Participants	182 Participants

Adverse Events

Capecitabine

Serious events: 181 serious events

Other events: 838 other events

Deaths: 0 deaths

5-Fluorouracil + Leucovorin

Serious events: 182 serious events

Other events: 847 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 616878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Capecitabine n=995 participants at risk Participants received capecitabine 1250 (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).	5-Fluorouracil + Leucovorin n=974 participants at risk 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).
General disorders Lethargy	9.7% 97/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	9.4% 92/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Gastrointestinal disorders Diarrhoea	43.9% 437/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	62.6% 610/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Gastrointestinal disorders Nausea	33.6% 334/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	47.1% 459/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Gastrointestinal disorders Stomatitis all	21.9% 218/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	58.9% 574/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Gastrointestinal disorders Vomiting	14.8% 147/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	20.4% 199/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Gastrointestinal disorders Abdominal pain	13.4% 133/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	15.3% 149/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Gastrointestinal disorders Constipation	8.6% 86/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	10.6% 103/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Gastrointestinal disorders Abdominal pain upper	7.0% 70/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	6.7% 65/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Gastrointestinal disorders Dyspepsia	5.9% 59/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	4.9% 48/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Palmar-plantar	59.6% 593/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	8.7% 85/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Erythrodysaesthesia syndrome Alopecia	6.3% 63/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	22.4% 218/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Rash	7.0% 70/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	8.2% 80/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Erythema	5.8% 58/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	5.2% 51/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
General disorders Fatigue	15.6% 155/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	15.4% 150/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
General disorders Asthenia	9.6% 96/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	9.8% 95/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
General disorders Pyrexia	6.8% 68/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	8.0% 78/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Nervous system disorders Dysgeusia	5.9% 59/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	9.1% 89/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Nervous system disorders Headache	5.1% 51/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	6.1% 59/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Metabolism and nutrition disorders Anorexia	9.0% 90/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	10.7% 104/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Eye disorders Conjunctivitis	4.7% 47/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	6.2% 60/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.
Nervous system disorders Dizziness	6.2% 62/995 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.	5.5% 54/974 • Up to Week 29 Adverse event is reported for safety population which consist of all participants who received at least one dose of capecitabine, 5-fluorouracil, or leucovorin and had at least one post baseline safety assessment.