Trial Outcomes & Findings for Lapatinib in Combination With Capecitabine in Japanese Patients With Metastatic Breast Cancer (NCT NCT00477464)
NCT ID: NCT00477464
Last Updated: 2018-09-17
Results Overview
CBR is defined as the percentage of participants receiving at least one dose of study medication who achieved a best overall response classified as a complete or partial (confirmed) tumor response or stable disease for at least 6 months (24 weeks). A "complete response" is defined as the disappearance of all target or non-target lesions, "partial response" and "disease progression" as at least a 30% decrease and at least a 20% increase, respectively, in the sum of the longest diameter of target lesions, and "stable disease" as neither "partial response" nor "disease progression."
COMPLETED
PHASE2
51 participants
Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression (up to Week 119)
2018-09-17
Participant Flow
Participant milestones
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Overall Study
STARTED
|
51
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
51
|
Reasons for withdrawal
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
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|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Death
|
36
|
|
Overall Study
Completion of protocol-defined follow-up
|
14
|
Baseline Characteristics
Lapatinib in Combination With Capecitabine in Japanese Patients With Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=51 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Age, Continuous
|
55.5 Years
STANDARD_DEVIATION 8.85 • n=5 Participants
|
|
Sex: Female, Male
Female
|
51 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
|
51 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression (up to Week 119)Population: Intent-to-treat (ITT) Population: participants who had received at least one dose of study medication.
CBR is defined as the percentage of participants receiving at least one dose of study medication who achieved a best overall response classified as a complete or partial (confirmed) tumor response or stable disease for at least 6 months (24 weeks). A "complete response" is defined as the disappearance of all target or non-target lesions, "partial response" and "disease progression" as at least a 30% decrease and at least a 20% increase, respectively, in the sum of the longest diameter of target lesions, and "stable disease" as neither "partial response" nor "disease progression."
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=51 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
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|---|---|
|
Clinical Benefit Response (Independent Reviewer-assessed)
|
59 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death due to breast cancer (up to Week 119)Population: ITT Population
Time to progression is defined as the interval between the start of treatment and the earliest date of disease progression or death due to breast cancer, if sooner. Time to progression was calculated by using the Kaplan Meier estimate.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=51 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
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|---|---|
|
Time to Progression (Independent Reviewer-assessed)
|
36.0 weeks
Interval 27.1 to 48.0
|
SECONDARY outcome
Timeframe: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)Population: ITT Population
PFS is defined as the interval between the start of treatment and the earliest date of disease progression or death of any cause, if sooner.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=51 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Progression-free Survival (PFS) (Independent Reviewer-assessed)
|
36.0 weeks
Interval 27.1 to 48.0
|
SECONDARY outcome
Timeframe: Baseline and then every 6 weeks until Month 6 (Week 24)Population: ITT Population
6-Month progression-free survival is defined as the percentage of participants surviving without progressive disease at 6 months (24 weeks) after the start of treatment. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=51 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
6-Month Progression-free Survival (Independent Reviewer-assessed)
|
68.2 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)Population: ITT Population
Objective response is defined as the percentage of participants achieving a best overall response classified as a complete or partial (confirmed) tumor response. Complete response is defined as the disappearance of all target or non-target lesions, and partial response is defined as at least a 30% decrease in the sum of the longest diameter of target lesions.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=51 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Objective Response (Independent Reviewer-assessed)
|
24 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and then followed every 4 weeks until death (up to Week 157.9) while on treatment. After treatment termination, followed every 12 weeks until death (up to Week 157.9)Population: ITT Population
Overall survival is defined as the time from the start of treatment until death regardless of cause. For participants who did not die, time to death was censored at the time of last confirmation of survival.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=51 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
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|---|---|
|
Overall Survival (Independent Reviewer-assessed)
|
78.6 weeks
Interval 51.6 to 103.0
|
SECONDARY outcome
Timeframe: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)Population: Participants in the ITT Population achieving a partial or complete response
Time to response is defined as the time from the start of treatment until the first documented evidence of complete response or partial response.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=12 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
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|---|---|
|
Time to Response (Independent Reviewer-assessed)
|
6.9 weeks
Interval 5.4 to 11.6
|
SECONDARY outcome
Timeframe: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)Population: Participants in the ITT Population achieving a partial or complete response
For the subset of participants who showed a complete or partial response, duration of response is defined as the time from the first documented evidence of partial or complete tumor response until the first documented sign of disease progression or death due to breast cancer, if sooner.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=12 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
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|---|---|
|
Duration of Response (Independent Reviewer-assessed)
|
42.7 weeks
Interval 26.9 to 68.4
|
SECONDARY outcome
Timeframe: Week 2Population: PK Population: consisted of the first six participants who were enrolled into the study and evaluable for the PK parameters of the investigational products. One participant was excluded due to dose reduction.
Pharmacokinetic (PK) samples were collected at pre-dose, and at 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, 10, 12, and 24 hours (hr) (plus or minus 30 minutes) after dosing. Cmax is defined as the maximum concentration of lapatinib.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=5 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Maximum Plasma Concentration (Cmax) of Lapatinib
|
3520.872 nanograms/milliliter (ng/ml)
Interval 2570.46 to 4822.694
|
SECONDARY outcome
Timeframe: Week 2Population: PK Population. One participant was excluded due to dose reduction.
PK samples were collected at pre-dose, and at 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, 10, 12, and 24 hr (plus or minus 30 minutes) after dosing. Tmax is defined as the time to peak concentration from initiation of lapatinib dosing.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=5 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Time to Maximum Plasma Concentration (Tmax) of Lapatinib
|
4.727 hr
Interval 3.264 to 6.847
|
SECONDARY outcome
Timeframe: Week 2Population: PK Population. One participant was excluded due to dose reduction.
Terminal elimination half-life is defined as the duration until observation of half of the maximum concentration. PK samples were collected at pre-dose, and at 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, 10, 12, and 24 hr (plus or minus 30 minutes) after dosing.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=5 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Terminal Elimination Half-life (t1/2) of Lapatinib
|
11.948 hr
Interval 9.267 to 15.405
|
SECONDARY outcome
Timeframe: Week 2Population: PK Population. One participant was excluded due to dose reduction.
PK samples were collected at pre-dose, and at 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, 10, 12, and 24 hr (plus or minus 30 minutes) after dosing. AUC is defined as the area under the concentration-time curve from 0 to last quantifiable concentration (AUC 0-tau). AUC is a measure of exposure.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=5 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Area Under the Plasma Concentration-time Curve Within the Dosing Interval AUC0-tau of Lapatinib
|
48153.776 hr*ng/ml
Interval 34575.918 to 67063.618
|
SECONDARY outcome
Timeframe: Week 2Population: PK Population. One participant was excluded due to dose reduction.
PK samples were collected at pre-dose, and at 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, 10, 12, and 24 hr (plus or minus 30 minutes) after dosing. AUC is defined as the area under the concentration-time curve from 0 to 24 hour after dosing (AUC 0-24). AUC is a measure of exposure.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=5 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Area Under the Plasma Concentration-time Curve From Zero to 24 Hours AUC0-24 of Lapatinib
|
48063.990 hr*ng/ml
Interval 34431.61 to 67093.788
|
SECONDARY outcome
Timeframe: Week 2Population: PK Population. One participant was excluded due to dose reduction.
PK samples were collected at pre-dose, and at 0.5 (plus or minus 5 minutes), 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, and 10 hr (plus or minus 30 minutes) after dosing. Cmax is defined as the maximum concentration of drug. 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=5 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Cmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
Capecitabine
|
2698.033 ng/ml
Interval 1491.563 to 4880.371
|
|
Cmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
5-FU
|
282.967 ng/ml
Interval 127.386 to 628.562
|
|
Cmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
FBAL
|
5771.578 ng/ml
Interval 4999.139 to 6663.37
|
SECONDARY outcome
Timeframe: Week 2Population: PK Population. One participant was excluded due to dose reduction.
PK samples were collected at pre-dose, and at 0.5 (plus or minus 5 minutes), 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, and 10 hr (plus or minus 30 minutes) after dosing. Tmax is defined as the time to peak concentration from initiation of dosing. 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=5 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Tmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
Capecitabine
|
1.305 hr
Interval 0.48 to 3.544
|
|
Tmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
5-FU
|
1.305 hr
Interval 0.48 to 3.544
|
|
Tmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
FBAL
|
2.899 hr
Interval 1.862 to 4.514
|
SECONDARY outcome
Timeframe: Week 2Population: PK Population. One participant was excluded due to dose reduction.
Terminal elimination half-life is defined as the duration until observation of half of the maximum concentration. PK samples were collected at pre-dose, and at 0.5 (plus or minus 5 minutes), 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, and 10 hr (plus or minus 30 minutes) after dosing. 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=5 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
t1/2 of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
Capecitabine
|
0.865 hr
Interval 0.438 to 1.709
|
|
t1/2 of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
5-FU
|
0.838 hr
Interval 0.572 to 1.229
|
|
t1/2 of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
FBAL
|
2.437 hr
Interval 2.1 to 2.828
|
SECONDARY outcome
Timeframe: Week 2Population: PK Population. One participant was excluded due to dose reduction.
PK samples were collected at pre-dose, and at 0.5 (plus or minus 5 minutes), 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, and 10 hr (plus or minus 30 minutes) after dosing. AUC is defined as the area under the concentration-time curve from 0 to last quantifiable concentration (AUC 0-tau). 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=5 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
AUC0-tau of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
Capecitabine
|
3997.313 hr*ng/ml
Interval 3008.973 to 5310.288
|
|
AUC0-tau of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
5-FU
|
514.670 hr*ng/ml
Interval 349.554 to 757.782
|
|
AUC0-tau of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
FBAL
|
29035.744 hr*ng/ml
Interval 26354.157 to 31990.189
|
SECONDARY outcome
Timeframe: Week 2Population: PK Population. One participant was excluded due to dose reduction.
PK samples were collected at pre-dose, and at 0.5 (plus or minus 5 minutes), 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, and 10 hr (plus or minus 30 minutes) after dosing. AUC is defined as the area under the concentration-time curve from 0 to 12 hours after dosing (AUC 0-12). 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=5 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Area Under the Plasma Concentration-time Curve From Zero to 12 Hours (AUC0-12) of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
Capecitabine
|
3999.383 hr*ng/ml
Interval 3011.222 to 5311.818
|
|
Area Under the Plasma Concentration-time Curve From Zero to 12 Hours (AUC0-12) of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
5-FU
|
544.318 hr*ng/ml
Interval 366.956 to 807.405
|
|
Area Under the Plasma Concentration-time Curve From Zero to 12 Hours (AUC0-12) of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
FBAL
|
30478.416 hr*ng/ml
Interval 27682.239 to 33557.034
|
SECONDARY outcome
Timeframe: Week 2Population: ITT Population. Evaluable samples were not taken from some participants.
PK samples were collected at pre-dose on Day 14 and Day 21 (minus 2 days). Trough concentration is defined as the minimum serum concentration at steady state after a repeated dose of lapatinib.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=42 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Trough Concentration of Lapatinib
Week 2, n=42
|
1065.558 ng/ml
Standard Deviation 718.6293
|
|
Trough Concentration of Lapatinib
Week 3, n=41
|
1243.540 ng/ml
Standard Deviation 849.3387
|
SECONDARY outcome
Timeframe: Week 2Population: ITT Population. Evaluable samples were not taken from some participants.
PK samples were collected at pre-dose on Day 14 (minus 2 days). Trough concentration is defined as the minimum serum concentration at steady state after a repeated dose. 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.
Outcome measures
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=42 Participants
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Trough Concentration of Capecitabine, 5-FU, and FBAL
Capecitabine
|
NA ng/ml
Standard Deviation NA
A mean cannot be calculated because the concentration was below the quantification limit.
|
|
Trough Concentration of Capecitabine, 5-FU, and FBAL
5-FU
|
NA ng/ml
Standard Deviation NA
A mean cannot be calculated because the concentration was below the quantification limit.
|
|
Trough Concentration of Capecitabine, 5-FU, and FBAL
FBAL
|
668.73 ng/ml
Standard Deviation 456.403
|
Adverse Events
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
Serious adverse events
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=51 participants at risk
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Cardiac disorders
Left ventricular dysfunction
|
3.9%
2/51
|
|
Cardiac disorders
Pericardial effusion
|
2.0%
1/51
|
|
Blood and lymphatic system disorders
Bone marrow failure
|
2.0%
1/51
|
|
Ear and labyrinth disorders
Vertigo
|
2.0%
1/51
|
|
Gastrointestinal disorders
Dysphagia
|
2.0%
1/51
|
|
Infections and infestations
Pulmonary tuberculosis
|
2.0%
1/51
|
|
Investigations
Neutrophil count decreased
|
2.0%
1/51
|
|
Nervous system disorders
Syncope
|
2.0%
1/51
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.0%
1/51
|
Other adverse events
| Measure |
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
n=51 participants at risk
Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m\^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.9%
3/51
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.8%
4/51
|
|
Gastrointestinal disorders
Cheilitis
|
13.7%
7/51
|
|
Gastrointestinal disorders
Constipation
|
9.8%
5/51
|
|
Gastrointestinal disorders
Diarrhoea
|
66.7%
34/51
|
|
Gastrointestinal disorders
Nausea
|
33.3%
17/51
|
|
Gastrointestinal disorders
Stomach discomfort
|
7.8%
4/51
|
|
Gastrointestinal disorders
Stomatitis
|
41.2%
21/51
|
|
Gastrointestinal disorders
Vomiting
|
11.8%
6/51
|
|
General disorders
Fatigue
|
33.3%
17/51
|
|
General disorders
Malaise
|
11.8%
6/51
|
|
General disorders
Pyrexia
|
17.6%
9/51
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
5.9%
3/51
|
|
Infections and infestations
Cellulitis
|
5.9%
3/51
|
|
Infections and infestations
Cystitis
|
5.9%
3/51
|
|
Infections and infestations
Nasopharyngitis
|
29.4%
15/51
|
|
Infections and infestations
Paronychia
|
27.5%
14/51
|
|
Investigations
Alanine aminotransferase increased
|
29.4%
15/51
|
|
Investigations
Aspartate aminotransferase increased
|
29.4%
15/51
|
|
Investigations
Blood albumin decreased
|
9.8%
5/51
|
|
Investigations
Blood alkaline phosphatase increased
|
15.7%
8/51
|
|
Investigations
Blood bilirubin increased
|
31.4%
16/51
|
|
Investigations
Haematocrit decreased
|
5.9%
3/51
|
|
Investigations
Haemoglobin decreased
|
7.8%
4/51
|
|
Investigations
Lymphocyte count decreased
|
7.8%
4/51
|
|
Investigations
Neutrophil count decreased
|
21.6%
11/51
|
|
Investigations
Platelet count decreased
|
7.8%
4/51
|
|
Investigations
Red blood cell count decreased
|
15.7%
8/51
|
|
Investigations
Weight decreased
|
13.7%
7/51
|
|
Investigations
White blood cell count decreased
|
27.5%
14/51
|
|
Investigations
White blood cell count increased
|
5.9%
3/51
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
17/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
11.8%
6/51
|
|
Nervous system disorders
Dizziness
|
11.8%
6/51
|
|
Nervous system disorders
Headache
|
13.7%
7/51
|
|
Psychiatric disorders
Insomnia
|
7.8%
4/51
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.8%
4/51
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.9%
3/51
|
|
Skin and subcutaneous tissue disorders
Acne
|
9.8%
5/51
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
29.4%
15/51
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.9%
3/51
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
7.8%
4/51
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
7.8%
4/51
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
9.8%
5/51
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
76.5%
39/51
|
|
Skin and subcutaneous tissue disorders
Pigmentation disorder
|
17.6%
9/51
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
33.3%
17/51
|
|
Skin and subcutaneous tissue disorders
Rash
|
39.2%
20/51
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
13.7%
7/51
|
|
Vascular disorders
Flushing
|
5.9%
3/51
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER