Lapatinib in Combination With Capecitabine in Japanese Pa... | NCT00477464

Label	Type	Description	Intervention Names
Lapatinib+capecitabine	Experimental	Lapatinib 1250mg once daily +capecitabine 2000mg/m^2 twice daily (14 days out of 21 days)	Drug: Lapatinib Drug: capecitabine

Name	Type	Description	Arm Group Labels	Other Names
Lapatinib	Drug	1250mg once daily	Lapatinib+capecitabine
capecitabine

Measure	Description	Time Frame
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."	Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression (up to Week 119)

Measure	Description	Time Frame
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.	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)

Eligibility Module

Eligibility Criteria

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:

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).

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Aichi		464-8681	Japan
GSK Investigational Site

ID	Title	Description
FG000	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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."

Intent-to-treat (ITT) Population: participants who had received at least one dose of study medication.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG00051

Title

Denominators

Categories

Title	Measurements
	OG00059

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000						percentage of participants	59			2-Sided	95	44.2	72.4			The estimated value represents the percentage of participants who achieved a best overall response of complete response, partial response, or stable disease.		Superiority or Other

Secondary

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.

ITT Population

Posted

Median

95% Confidence Interval

weeks

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)

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

ITT Population

Posted

Median

95% Confidence Interval

weeks

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

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

ITT Population

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

ITT Population

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

ITT Population

Posted

Median

95% Confidence Interval

weeks

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)

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

Participants in the ITT Population achieving a partial or complete response

Posted

Median

95% Confidence Interval

weeks

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

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

Participants in the ITT Population achieving a partial or complete response

Posted

Median

95% Confidence Interval

weeks

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

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

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.

Posted

Geometric Mean

95% Confidence Interval

nanograms/milliliter (ng/ml)

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

PK Population. One participant was excluded due to dose reduction.

Posted

Geometric Mean

95% Confidence Interval

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

PK Population. One participant was excluded due to dose reduction.

Posted

Geometric Mean

95% Confidence Interval

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

PK Population. One participant was excluded due to dose reduction.

Posted

Geometric Mean

95% Confidence Interval

hr*ng/ml

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

PK Population. One participant was excluded due to dose reduction.

Posted

Geometric Mean

95% Confidence Interval

hr*ng/ml

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

PK Population. One participant was excluded due to dose reduction.

Posted

Geometric Mean

95% Confidence Interval

ng/ml

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

PK Population. One participant was excluded due to dose reduction.

Posted

Geometric Mean

95% Confidence Interval

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2

Units	Counts
Participants	OG000

Secondary

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.

PK Population. One participant was excluded due to dose reduction.

Posted

Geometric Mean

95% Confidence Interval

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

PK Population. One participant was excluded due to dose reduction.

Posted

Geometric Mean

95% Confidence Interval

hr*ng/ml

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

PK Population. One participant was excluded due to dose reduction.

Posted

Geometric Mean

95% Confidence Interval

hr*ng/ml

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants

Secondary

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.

ITT Population. Evaluable samples were not taken from some participants.

Posted

Mean

Standard Deviation

ng/ml

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

ITT Population. Evaluable samples were not taken from some participants.

Posted

Mean

Standard Deviation

ng/ml

Week 2

ID	Title	Description
OG000	Lapatinib 1250 mg and Capecitabine 2000 mg/m^2	Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 mg once daily. Capecitabine was orally administered at 1000 mg/m^2 twice daily on the first day through the fourteenth day of each 21-day cycle.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected51 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected51 at risk
Cheilitis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0007 affected51 at risk
Constipation	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected51 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00034 affected51 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00017 affected51 at risk
Stomach discomfort	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected51 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00021 affected51 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0006 affected51 at risk
Fatigue	General disorders	MedDRA 10.0	Systematic Assessment	EG00017 affected51 at risk
Malaise	General disorders	MedDRA 10.0	Systematic Assessment	EG0006 affected51 at risk
Pyrexia	General disorders	MedDRA 10.0	Systematic Assessment	EG0009 affected51 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected51 at risk
Cellulitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0003 affected51 at risk
Cystitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0003 affected51 at risk
Nasopharyngitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG00015 affected51 at risk
Paronychia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG00014 affected51 at risk
Alanine aminotransferase increased	Investigations	MedDRA 10.0	Systematic Assessment	EG00015 affected51 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 10.0	Systematic Assessment	EG00015 affected51 at risk
Blood albumin decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0005 affected51 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0008 affected51 at risk
Blood bilirubin increased	Investigations	MedDRA 10.0	Systematic Assessment	EG00016 affected51 at risk
Haematocrit decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0003 affected51 at risk
Haemoglobin decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0004 affected51 at risk
Lymphocyte count decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0004 affected51 at risk
Neutrophil count decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG00011 affected51 at risk
Platelet count decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0004 affected51 at risk
Red blood cell count decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0008 affected51 at risk
Weight decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0007 affected51 at risk
White blood cell count decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG00014 affected51 at risk
White blood cell count increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0003 affected51 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG00017 affected51 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0006 affected51 at risk
Dizziness	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0006 affected51 at risk
Headache	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0007 affected51 at risk
Insomnia	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected51 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected51 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected51 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected51 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00015 affected51 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected51 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected51 at risk
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected51 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected51 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00039 affected51 at risk
Pigmentation disorder	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0009 affected51 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00017 affected51 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00020 affected51 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0007 affected51 at risk
Flushing	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected51 at risk

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D005472	Fluorouracil
D014498	Uracil
D011744	Pyrimidinones
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Left ventricular dysfunction	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected51 at risk
Pericardial effusion	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected51 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected51 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected51 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected51 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected51 at risk
Neutrophil count decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 affected51 at risk
Syncope	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected51 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected51 at risk