Lapatinib in Combination With Capecitabine in Japanese Patients With Metastatic Breast Cancer
- Conditions
- Neoplasms, BreastMetastatic Breast Cancer
- Interventions
- Registration Number
- NCT00477464
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This study is to evaluate the safety and efficacy of lapatinib taken together with capecitabine in Japanese patients. The study will proceed in two phases; the first phase(Part1) will lead to an evaluation of the mainly tolerability as well as PK parameters. If there are no major safety concerns in Part 1, the study will move into the second phase (Part 2) to further evaluate the safety and clinical activity.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 51
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Lapatinib+capecitabine capecitabine Lapatinib 1250mg once daily +capecitabine 2000mg/m\^2 twice daily (14 days out of 21 days) Lapatinib+capecitabine Lapatinib Lapatinib 1250mg once daily +capecitabine 2000mg/m\^2 twice daily (14 days out of 21 days)
- Primary Outcome Measures
Name Time Method Clinical Benefit Response (Independent Reviewer-assessed) Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression (up to Week 119) 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."
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) (Independent Reviewer-assessed) Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119) 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.
Area Under the Plasma Concentration-time Curve From Zero to 24 Hours AUC0-24 of Lapatinib Week 2 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.
Overall Survival (Independent Reviewer-assessed) 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) 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.
Maximum Plasma Concentration (Cmax) of Lapatinib Week 2 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.
Time to Response (Independent Reviewer-assessed) Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119) Time to response is defined as the time from the start of treatment until the first documented evidence of complete response or partial response.
Trough Concentration of Lapatinib Week 2 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.
Terminal Elimination Half-life (t1/2) of Lapatinib Week 2 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.
AUC0-tau of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL) Week 2 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.
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) Week 2 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.
Time to Progression (Independent Reviewer-assessed) 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) 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.
6-Month Progression-free Survival (Independent Reviewer-assessed) Baseline and then every 6 weeks until Month 6 (Week 24) 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.
Objective Response (Independent Reviewer-assessed) Baseline every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119) 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.
Duration of Response (Independent Reviewer-assessed) Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119) 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.
Tmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL) Week 2 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.
Time to Maximum Plasma Concentration (Tmax) of Lapatinib Week 2 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.
Area Under the Plasma Concentration-time Curve Within the Dosing Interval AUC0-tau of Lapatinib Week 2 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.
Cmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL) Week 2 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.
Trough Concentration of Capecitabine, 5-FU, and FBAL Week 2 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.
t1/2 of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL) Week 2 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.
Trial Locations
- Locations (1)
GSK Investigational Site
🇯🇵Tokyo, Japan