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CompletedNCT00477464Updated Sep 17, 2018Results posted

Lapatinib in Combination With Capecitabine in Japanese Patients With Metastatic Breast Cancer

A Phase 2 interventional study of Lapatinib and capecitabine in Metastatic Breast Cancer and Neoplasms, Breast, sponsored by GlaxoSmithKline. Completed at 15 sites in Japan. Open to female participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2018-09-17.

Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
51
Allocation
Non-randomized
Ages
20 Years and older
Sex
Female
01

Study 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.

02

Conditions studied

  • Metastatic Breast Cancer
  • Neoplasms, Breast

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Keywords

  • dual kinase inhibitor,
  • EGFR/ErbB1,
  • ErbB2-overexpressing,
  • GW572016,
  • advanced/metastatic breast cancer, Lapatinib,
  • HER-2/new,
  • pharmacokinetics
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 51 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Subjects eligible for enrolment in the study must meet all of the following criteria:
  • Patients who have consent to this study participation and signed into Informed consent form.
  • Subjects must have histologically confirmed invasive breast cancer with stage IIIB, stage IIIC with T4 lesion, or stage IV disease.
  • Documentation of ErbB2 overexpression [IHC3+ or IHC2+ with FISH confirmation] is required based on local laboratory.
  • Subjects must have documented progressive advanced or metastatic breast cancer.
  • Subjects must have refractory breast cancer defined as progression in the locally advanced or metastatic setting or relapse within 6 months of completing adjuvant therapy. Prior therapies must include, but are not limited to:
  • Taxane containing regimen for at least 4 cycles or 2 cycles provided disease progression occurred while on taxane.
  • Anthracycline containing regimen for at least 4 cycles or 2 cycles provided disease progression occurred while on anthracycline.
  • Subjects who relapse >6 months after completion of adjuvant anthracycline-containing chemotherapy, and for whom further anthracycline is not indicated, will be considered to have met the anthracycline prior exposure requirement.
  • Taxanes and anthracyclines may have been administered concurrently or separately.
  • Prior treatment with capecitabine is not permitted.
  • Prior treatment must have contained trastuzumab alone or in combination with other chemotherapy for at least 6 weeks of standard doses in the adjuvant or advanced/metastatic setting.
  • Subjects with hormone receptor positive tumors must have disease progression following hormonal therapy unless intolerant to hormonal therapy or hormonal therapy is not considered to be clinically appropriate.
  • Subjects with stable CNS metastases (asymptomatic, and off systemic steroids and anticonvulsants for at least 3 months) are eligible.
  • Measurable disease according to modified RECIST (Response Evaluation Criteria in Solid Tumors) (see Section 6.2, Efficacy p.49).
  • Subjects must have archived tumor tissue available for biomarker assessment.
  • Female subjects must be ≥20
  • ECOG Performance Status of 0 or 1.
  • Life expectancy of ≥12 weeks.
  • Measurable lesions may be in the field of prior irradiation. However, there must be at least a 4-week period between the last radiation treatment and the baseline scan documenting disease status for the lesion to be measurable.
  • Cardiac ejection fraction within the institutional range of normal as measured by ECHO (or MUGA if ECHO is not available). If no institutional range is available, cardiac ejection fraction must be ≥50%.

  • Adequate hematologic value, hepatic and renal function as defined below. Hematologic ANC (absolute neutrophil count) ≥1.5×109/L Hemoglobin ≥9 g/dL Platelets ≥100× 109/L Hepatic Serum bilirubin ≤1.5×ULN

    • 2.5×ULN if subject has Gilbert's syndrome AST and ALT ≤5×ULN if documented liver metastases

    • 3×ULN without liver metastases Renal Serum creatinine Creatinine clearance* ≤50 mL/min

      • Calculated by the Cockcroft and Gault Method

Exclusion criteria

Exclusion criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

  • Pregnant or lactating females.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. In addition, subjects with ulcerative colitis are excluded.
  • History of other malignancy. Subjects who have been disease-free for at least 5 years or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior anticancer therapy.
  • Active or uncontrolled infection.
  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  • Known history of uncontrolled or symptomatic angina, arrhythmia or congestive heart failure.
  • No prior anti-ErbB1/ErbB2 inhibitor for breast cancer other than trastuzumab.
  • Known history or clinical evidence of leptomeningeal carcinomatosis.
  • Concurrent anticancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than capecitabine.
  • Bisphosphonates for the treatment of bone metastases should not be initiated following the first dose of study medication. Prophylactic use of bisphosphonate in subjects without bone disease is not permitted, except for prevention of osteoporosis.
  • Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication.
  • Participation in other studies or use of other investigational drugs during this study.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients of lapatinib.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to capecitabine, fluorouracil or any excipients.
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency.
  • Patients who an investigator judges ineligible to this study in consideration of patient's safety (e.g., complications).
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
51 participants (actual)

Study arms

  • Experimental
    Lapatinib+capecitabine

    Lapatinib 1250mg once daily +capecitabine 2000mg/m\^2 twice daily (14 days out of 21 days)

    Drug: Lapatinib · Drug: capecitabine

Interventions

  • DrugLapatinib

    1250mg once daily

  • Drugcapecitabine

    2000mg/m\^2 twice daily (14 days out of 21 days)

06

What researchers measure

Primary outcomes

  1. Clinical Benefit Response (Independent Reviewer-assessed)

    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."

    Time frame: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression (up to Week 119)

Secondary outcomes

  1. Time to Progression (Independent Reviewer-assessed)

    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.

    Time frame: 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)

  2. Progression-free Survival (PFS) (Independent Reviewer-assessed)

    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.

    Time frame: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)

  3. 6-Month Progression-free Survival (Independent Reviewer-assessed)

    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.

    Time frame: Baseline and then every 6 weeks until Month 6 (Week 24)

  4. Objective Response (Independent Reviewer-assessed)

    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.

    Time frame: Baseline every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)

  5. Overall Survival (Independent Reviewer-assessed)

    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.

    Time frame: 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)

  6. Time to Response (Independent Reviewer-assessed)

    Time to response is defined as the time from the start of treatment until the first documented evidence of complete response or partial response.

    Time frame: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)

  7. Duration of Response (Independent Reviewer-assessed)

    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.

    Time frame: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)

  8. Maximum Plasma Concentration (Cmax) of Lapatinib

    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 frame: Week 2

  9. Time to Maximum Plasma Concentration (Tmax) of Lapatinib

    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.

    Time frame: Week 2

  10. Terminal Elimination Half-life (t1/2) of Lapatinib

    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.

    Time frame: Week 2

  11. Area Under the Plasma Concentration-time Curve Within the Dosing Interval AUC0-tau of Lapatinib

    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.

    Time frame: Week 2

  12. Area Under the Plasma Concentration-time Curve From Zero to 24 Hours AUC0-24 of Lapatinib

    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.

    Time frame: Week 2

  13. Cmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

    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.

    Time frame: Week 2

  14. Tmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

    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 frame: Week 2

  15. t1/2 of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

    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.

    Time frame: Week 2

  16. AUC0-tau of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

    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.

    Time frame: Week 2

  17. 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)

    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 frame: Week 2

  18. Trough Concentration of Lapatinib

    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.

    Time frame: Week 2

  19. Trough Concentration of Capecitabine, 5-FU, and FBAL

    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.

    Time frame: Week 2

07

Results

Posted Sep 5, 2011

Participant flow

Participant flow — Overall Study
MilestoneLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Started51
Completed0
Not completed51
Withdrew: Lost to follow-up1
Withdrew: Death36
Withdrew: Completion of protocol-defined follow-up14

Outcome measures

PrimaryClinical Benefit Response (Independent Reviewer-assessed)

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."

Time frame:
Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression (up to Week 119)
Reported as:
Number · percentage of participants
Clinical Benefit Response (Independent Reviewer-assessed)
percentage of participantsLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Clinical Benefit Response (Independent Reviewer-assessed)59
Statistical analysis
  • Lapatinib 1250 mg and Capecitabine 2000 mg/m^2 · Percentage of participants: 59 · 95% CI 44.2 to 72.4The estimated value represents the percentage of participants who achieved a best overall response of complete response, partial response, or stable disease.
SecondaryTime to Progression (Independent Reviewer-assessed)

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.

Time frame:
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)
Reported as:
Median · weeks
Time to Progression (Independent Reviewer-assessed)
weeksLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Time to Progression (Independent Reviewer-assessed)36.0 (27.1 to 48.0)
SecondaryProgression-free Survival (PFS) (Independent Reviewer-assessed)

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.

Time frame:
Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)
Reported as:
Median · weeks
Progression-free Survival (PFS) (Independent Reviewer-assessed)
weeksLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Progression-free Survival (PFS) (Independent Reviewer-assessed)36.0 (27.1 to 48.0)
Secondary6-Month Progression-free Survival (Independent Reviewer-assessed)

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.

Time frame:
Baseline and then every 6 weeks until Month 6 (Week 24)
Reported as:
Number · percentage of participants
6-Month Progression-free Survival (Independent Reviewer-assessed)
percentage of participantsLapatinib 1250 mg and Capecitabine 2000 mg/m^2
6-Month Progression-free Survival (Independent Reviewer-assessed)68.2
SecondaryObjective Response (Independent Reviewer-assessed)

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.

Time frame:
Baseline every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)
Reported as:
Number · percentage of participants
Objective Response (Independent Reviewer-assessed)
percentage of participantsLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Objective Response (Independent Reviewer-assessed)24
SecondaryOverall Survival (Independent Reviewer-assessed)

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.

Time frame:
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)
Reported as:
Median · weeks
Overall Survival (Independent Reviewer-assessed)
weeksLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Overall Survival (Independent Reviewer-assessed)78.6 (51.6 to 103.0)
SecondaryTime to Response (Independent Reviewer-assessed)

Time to response is defined as the time from the start of treatment until the first documented evidence of complete response or partial response.

Time frame:
Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)
Reported as:
Median · weeks
Time to Response (Independent Reviewer-assessed)
weeksLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Time to Response (Independent Reviewer-assessed)6.9 (5.4 to 11.6)
SecondaryDuration of Response (Independent Reviewer-assessed)

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.

Time frame:
Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)
Reported as:
Median · weeks
Duration of Response (Independent Reviewer-assessed)
weeksLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Duration of Response (Independent Reviewer-assessed)42.7 (26.9 to 68.4)
SecondaryMaximum Plasma Concentration (Cmax) of Lapatinib

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 frame:
Week 2
Reported as:
Geometric mean · nanograms/milliliter (ng/ml)
Maximum Plasma Concentration (Cmax) of Lapatinib
nanograms/milliliter (ng/ml)Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
Maximum Plasma Concentration (Cmax) of Lapatinib3520.872 (2570.460 to 4822.694)
SecondaryTime to Maximum Plasma Concentration (Tmax) of Lapatinib

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.

Time frame:
Week 2
Reported as:
Geometric mean · hr
Time to Maximum Plasma Concentration (Tmax) of Lapatinib
hrLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Time to Maximum Plasma Concentration (Tmax) of Lapatinib4.727 (3.264 to 6.847)
SecondaryTerminal Elimination Half-life (t1/2) of Lapatinib

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.

Time frame:
Week 2
Reported as:
Geometric mean · hr
Terminal Elimination Half-life (t1/2) of Lapatinib
hrLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Terminal Elimination Half-life (t1/2) of Lapatinib11.948 (9.267 to 15.405)
SecondaryArea Under the Plasma Concentration-time Curve Within the Dosing Interval AUC0-tau of Lapatinib

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.

Time frame:
Week 2
Reported as:
Geometric mean · hr*ng/ml
Area Under the Plasma Concentration-time Curve Within the Dosing Interval AUC0-tau of Lapatinib
hr*ng/mlLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Area Under the Plasma Concentration-time Curve Within the Dosing Interval AUC0-tau of Lapatinib48153.776 (34575.918 to 67063.618)
SecondaryArea Under the Plasma Concentration-time Curve From Zero to 24 Hours AUC0-24 of Lapatinib

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.

Time frame:
Week 2
Reported as:
Geometric mean · hr*ng/ml
Area Under the Plasma Concentration-time Curve From Zero to 24 Hours AUC0-24 of Lapatinib
hr*ng/mlLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Area Under the Plasma Concentration-time Curve From Zero to 24 Hours AUC0-24 of Lapatinib48063.990 (34431.610 to 67093.788)
SecondaryCmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

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.

Time frame:
Week 2
Reported as:
Geometric mean · ng/ml
Cmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
ng/mlLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Capecitabine2698.033 (1491.563 to 4880.371)
5-FU282.967 (127.386 to 628.562)
FBAL5771.578 (4999.139 to 6663.370)
SecondaryTmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

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 frame:
Week 2
Reported as:
Geometric mean · hr
Tmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
hrLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Capecitabine1.305 (0.480 to 3.544)
5-FU1.305 (0.480 to 3.544)
FBAL2.899 (1.862 to 4.514)
Secondaryt1/2 of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

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.

Time frame:
Week 2
Reported as:
Geometric mean · hr
t1/2 of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
hrLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Capecitabine0.865 (0.438 to 1.709)
5-FU0.838 (0.572 to 1.229)
FBAL2.437 (2.100 to 2.828)
SecondaryAUC0-tau of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

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.

Time frame:
Week 2
Reported as:
Geometric mean · hr*ng/ml
AUC0-tau of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)
hr*ng/mlLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Capecitabine3997.313 (3008.973 to 5310.288)
5-FU514.670 (349.554 to 757.782)
FBAL29035.744 (26354.157 to 31990.189)
SecondaryArea 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)

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 frame:
Week 2
Reported as:
Geometric mean · hr*ng/ml
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)
hr*ng/mlLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Capecitabine3999.383 (3011.222 to 5311.818)
5-FU544.318 (366.956 to 807.405)
FBAL30478.416 (27682.239 to 33557.034)
SecondaryTrough Concentration of Lapatinib

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.

Time frame:
Week 2
Reported as:
Mean · ng/ml
Trough Concentration of Lapatinib
ng/mlLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Week 2, n=421065.558 ± 718.6293
Week 3, n=411243.540 ± 849.3387
SecondaryTrough Concentration of Capecitabine, 5-FU, and FBAL

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.

Time frame:
Week 2
Reported as:
Mean · ng/ml
Trough Concentration of Capecitabine, 5-FU, and FBAL
ng/mlLapatinib 1250 mg and Capecitabine 2000 mg/m^2
CapecitabineNA ± NA
5-FUNA ± NA
FBAL668.73 ± 456.403

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Lapatinib 1250 mg and Capecitabine 2000 mg/m^2—8/51 (15.7%)50/51 (98%)
Most frequent serious events
Most frequent serious events
EventLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Left ventricular dysfunctionCardiac disorders2/51
Pericardial effusionCardiac disorders1/51
Bone marrow failureBlood and lymphatic system disorders1/51
VertigoEar and labyrinth disorders1/51
DysphagiaGastrointestinal disorders1/51
Pulmonary tuberculosisInfections and infestations1/51
Neutrophil count decreasedInvestigations1/51
SyncopeNervous system disorders1/51
Respiratory failureRespiratory, thoracic and mediastinal disorders1/51
Most frequent other events
Showing 10 of 50
Most frequent other events
EventLapatinib 1250 mg and Capecitabine 2000 mg/m^2
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders39/51
DiarrhoeaGastrointestinal disorders34/51
StomatitisGastrointestinal disorders21/51
RashSkin and subcutaneous tissue disorders20/51
NauseaGastrointestinal disorders17/51
FatigueGeneral disorders17/51
AnorexiaMetabolism and nutrition disorders17/51
PruritusSkin and subcutaneous tissue disorders17/51
Blood bilirubin increasedInvestigations16/51
NasopharyngitisInfections and infestations15/51

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
Mean55.5 ± 8.85
Sex: Female, Male
Sex: Female, Male(Participants)Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
Female51
Male0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
Number51
08

Study locations

15 sites
  • GSK Investigational Site
    Aichi, 464-8681, Japan
  • GSK Investigational Site
    Chiba, 277-8577, Japan
  • GSK Investigational Site
    Ehime, 791-0280, Japan
  • GSK Investigational Site
    Fukuoka, 811-1395, Japan
  • GSK Investigational Site
    Hokkaido, 003-0804, Japan
  • GSK Investigational Site
    Ibaraki, 305-8576, Japan
  • GSK Investigational Site
    Kagoshima, 892-0833, Japan
  • GSK Investigational Site
    Osaka, 540-0006, Japan
  • GSK Investigational Site
    Osaka, 553-0003, Japan
  • GSK Investigational Site
    Shizuoka, 411-8777, Japan
  • GSK Investigational Site
    Tochigi, 329-0498, Japan
  • GSK Investigational Site
    Tokyo, 104-0045, Japan
  • GSK Investigational Site
    Tokyo, 104-8560, Japan
  • GSK Investigational Site
    Tokyo, 113-8677, Japan
  • GSK Investigational Site
    Tokyo, 135-8550, Japan
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 17, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00477464
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
May 23, 2007
Start date
Jun 2007
Primary completion
Dec 2010
Completion
Dec 2010
Results posted
Sep 5, 2011
Last update
Sep 17, 2018

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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