Brain Metastases In ErbB2-Positive Breast Cancer | NCT00437073

Label	Type	Description	Intervention Names
lapatinib plus capecitabine	Experimental	A total of 55 isubjects will be enrolled into this arm. Subjects with progression of CNS and/or non-CNS disease will be considered progressors. At the time of radiographically-documented CNS and/or non-CNS disease progression, a subject randomized to this arm will be allowed to cross over to the alternative arm.	Drug: capecitabine Drug: lapatinib
lapatinib + topotecan	Experimental	A total of 55 isubjects will be enrolled into this arm. Subjects with progression of CNS and/or non-CNS disease will be considered progressors. At the time of radiographically-documented CNS and/or non-CNS disease progression, a subject randomized to this arm will be allowed to cross over to the alternative arm.	Drug: topotecan Drug: lapatinib

Name	Type	Description	Arm Group Labels	Other Names
capecitabine	Drug	capecitabine 2000mg/m2/day orally, Days 1-14, every 21 days	lapatinib plus capecitabine

Measure	Description	Time Frame
Number of Participants With the Indicated Central Nervous System (CNS) Objective Response (OR)	CNS OR is defined as the number of participants with either a complete response (CR) or partial response (PR) as assessed by volumetric analysis of brain magnetic resonance imaging (MRI) and Response Evaluation Criteria In Solid Tumors (RECIST). CR: complete resolution of all evaluable and non-evaluable brain metastases; PR: =>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline.	From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
Number of Participants With the Indicated CNS Responses	CNS responses were assessed by volumetric (V) analysis of brain MRI and RECIST. CR: complete resolution of all evaluable and non-evaluable brain metastases (BMs). PR: =>50% reduction in the V sum of all evaluable BMs compared to baseline. A response of "Other" was used for participants who discontinued the study prior to the first efficacy assessment. Stable Disease (SD): disease that does not meet CR, PR, or CNS progression criteria. Progressive disease (PD): a requirement for a new steroid or an increasing steroid dose for the treatment of worsening neurological signs/symptoms due to BMs.	From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Measure	Description	Time Frame
Duration of CNS Objective Response (Defined as the Time From the First Documented Evidence of CNS PR or CR Until the First Documented Sign of Disease Progression or Death, if Sooner)	CNS OR is defined as the number of participants with either a CR or PR as assessed by volumetric analysis of brain MRI and RECIST. CR: complete resolution of all evaluable and non-evaluable brain metastases; PR: =>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Subjects eligible for enrollment in the study must meet all of the following criteria:

Signed written informed consent;
Females or males age ≥ 18 years old;
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1;
Life expectancy of at least 12 weeks;
Subjects must have histologically or cytologically confirmed invasive breast cancer, with Stage IV disease;
ErbB2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with ErbB 2 gene amplification by FISH, or ErbB 2 gene amplification by FISH alone (in subjects whose tumor blocks were not assessed by IHC). Subjects with tumors that are 2+ by IHC but negative or borderline by FISH assay are ineligible. For subjects with a history of more than one primary breast cancer, each breast cancer must be ErbB2 overexpressing to be eligible;
ErbB2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with ErbB2 gene amplification by FISH, or ErbB2 gene amplification by FISH alone (in subjects whose tumor blocks were not assessed by IHC). ErbB2 gene amplification is defined by: > 6 ErbB2 gene copies/nucleus for test systems without an internal control probe or an ErbB2/CEP 17 ratio of more than 2.2. Subjects with tumors that are 2+ by IHC but negative or borderline by FISH assay are ineligible. For subjects with a history of more than one primary breast cancer, each breast cancer must be ErbB2 overexpressing to be eligible;
Prior treatment of brain metastases with WBRT and/or SRS;
Unequivocal evidence of new and / or progressive lesions in the brain on an imaging study; Note: Subjects with progressive brain lesions are not required to meet RECIST criteria for CNS progression in order to be eligible for this study.
Prior treatment with trastuzumab, either alone or in combination with chemotherapy is required. Trastuzumab will be discontinued at least 2 weeks prior to enrollment on study;
Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. Subjects who require cardiac medications (e.g. positive inotropic agents or afterload reducers) for normal ejection fraction are ineligible. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive;
At least 2 weeks since prior radiotherapy, last chemotherapy, immunotherapy, biologic therapy, or hormonal therapy for cancer, and sufficiently recovered or stabilized from side effects associated with prior therapy. Concurrent treatment with bisphosphonates is permitted;
At least 3 weeks since major surgical procedures;
Able to swallow and retain oral medications;
Women of childbearing potential must have a negative serum pregnancy test at screening and must use an approved contraceptive method, if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product. Males able to father a child must practice adequate methods of birth control or practice complete abstinence from intercourse from the first dose of investigational treatment until one week after the final dose of investigational treatment.
Subjects must complete all screening assessments as outlined in the protocol;
Normal organ and marrow function as defined by these LABORATORY VALUES : ANC (absolute neutrophil count) ≥ 1.5 x 10^9/L; Hemoglobin ≥ 10 g/dL (after transfusion if needed); Platelets ≥ 100 x 10^9/L; Albumin ≥ 2.5 g/dL; Serum bilirubin ≤ 1.5x ULN unless due to Gilbert's syndrome; AST and ALT ≤ 5x ULN if documented liver metastases ≤ 3x ULN without liver metastases; Serum Creatinine ≤ 1.2 mg/dL or Calculated Creatinine Clearance1 ≥ 50 mL/min

Exclusion Criteria:

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

Subjects who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or who have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
Concurrent treatment with an investigational agent or participation in another treatment clinical trial;
Prior therapy with a topoisomerase 1 inhibitor;
Prior lapatinib therapy;
Prior therapy with capecitabine;
Known dihydropyrimidine dehydrogenase (DPD) deficiency;
ECOG Performance Status 2 or greater;
Subjects receiving concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of their cancer. Hormone therapy for ovarian suppression which has been used for > 6 months, during which time there has been disease progression in the brain, is allowed. Concurrent treatment with bisphosphonates is allowed;
Subjects with evidence of leptomeningeal carcinomatosis at screening;
History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib;
History of allergic reactions attributed to compounds chemically related to capecitabine, fluorouracil or any excipients;
Concurrent treatment with medications listed as Prohibited Medications;
Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded;
History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast;
Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel;
Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety;
Anticoagulant therapy (other than coumadin or aspirin as catheter prophylaxis) at study entry;
Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent, unless a legally acceptable representative could provide informed consent (if in accord with the policies of the local Ethics Committee);
Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel, CNS vasculitis, or malignant hypertension;
Active cardiac disease, defined as one or more of the following:
History of uncontrolled or symptomatic angina
History of arrhythmias requiring medications, or clinically significant
Myocardial infarction < 6 months from study entry
Uncontrolled or symptomatic congestive heart failure
Ejection fraction below the institutional normal limit
Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient;
Uncontrolled infection;
Pregnant or lactating females;
History of other malignancy, except for curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. Subjects with other malignancies who have been disease-free for at least 5 years are eligible.
Have current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Washington D.C.	District of Columbia	20007	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
21706359	Background	Lin NU, Eierman W, Greil R, Campone M, Kaufman B, Steplewski K, Lane SR, Zembryki D, Rubin SD, Winer EP. Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. J Neurooncol. 2011 Dec;105(3):613-20. doi: 10.1007/s11060-011-0629-y. Epub 2011 Jun 26.

ID	Title	Description
FG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.

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

Number of Participants With the Indicated Central Nervous System (CNS) Objective Response (OR)

CNS OR is defined as the number of participants with either a complete response (CR) or partial response (PR) as assessed by volumetric analysis of brain magnetic resonance imaging (MRI) and Response Evaluation Criteria In Solid Tumors (RECIST). CR: complete resolution of all evaluable and non-evaluable brain metastases; PR: =>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline.

Modified Intent-to-Treat (mITT) Population: all participants who had at least one evaluable CNS target lesion at baseline and who had received at least two doses of lapatinib medication

Posted

Number

participants

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Units	Counts
Participants	OG00013 OG0019

Title

Denominators

Categories

Title	Measurements
	OG0005 OG0010

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	38			2-Sided	95	13.9	68.4			The estimated value indicates the percentage of participants with CNS OR in the Lapatinib plus Capecitabine treatment arm.	No	Superiority or Other

Primary

Number of Participants With the Indicated CNS Responses

CNS responses were assessed by volumetric (V) analysis of brain MRI and RECIST. CR: complete resolution of all evaluable and non-evaluable brain metastases (BMs). PR: =>50% reduction in the V sum of all evaluable BMs compared to baseline. A response of "Other" was used for participants who discontinued the study prior to the first efficacy assessment. Stable Disease (SD): disease that does not meet CR, PR, or CNS progression criteria. Progressive disease (PD): a requirement for a new steroid or an increasing steroid dose for the treatment of worsening neurological signs/symptoms due to BMs.

mITT Population

Posted

Number

participants

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Secondary

Duration of CNS Objective Response (Defined as the Time From the First Documented Evidence of CNS PR or CR Until the First Documented Sign of Disease Progression or Death, if Sooner)

CNS OR is defined as the number of participants with either a CR or PR as assessed by volumetric analysis of brain MRI and RECIST. CR: complete resolution of all evaluable and non-evaluable brain metastases; PR: =>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

mITT Population

Posted

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Secondary

Percentage of Participants With Clinical Benefit

Clinical benefit is defined as CR (complete resolution of all evaluable and non-evaluable brain metastases), PR (=>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline), or stable disease (disease that does not meet CR, PR, or CNS progression criteria) for at least 6 months. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

mITT Population

Posted

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Secondary

Percentage of Participants (Par.) With Objective Response by RECIST in Non-CNS Disease

Non-CNS disease (for par. with measurable baseline non-CNS disease) OR is defined as the number of par. with either a CR or PR as assessed by computed tomography (CT) or MRI scan and RECIST. CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough par. enrolled in the study to provide statistically valid analyses.

mITT Population

Posted

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Secondary

Time to CNS Objective Response (Defined as the Time From the Start of Treatment Until the First Documented Evidence of Partial or Complete Tumor Response [Whichever Status is Recorded First])

mITT Population

Posted

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan

Secondary

Number of Participants With the Indicated Site of Initial Disease Progression

The site of initial disease will be determined by taking the earliest date of known progression and assigning the appropriate category (CNS or non-CNS) based on the source of the earliest date. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

mITT Population

Posted

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Secondary

Progression-free Survival

Progression-free survival is defined as the time from the start of treatment until the first documented sign of disease progression at any site or death due to any cause, if sooner. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

mITT Population

Posted

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Secondary

Overall Survival

Overall survival is defined as the time from the start of treatment until death due to any cause. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

mITT Population

Posted

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Secondary

Percentage of Participants With Baseline Tumor-related (TR) Neurological Signs and Symptoms (NSS), Who Experienced Improvement in NSS as Measured by the Neurological Examination Worksheet (NEW)

TR NSS was to be recorded by the Investigator on the NEW, using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE V3.0). Improvement was to be defined as a decrease of 1 or more CTCAE grades from baseline of any TR NSS. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

mITT Population

Posted

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Secondary

Percentage of Participants With Disease Stabilization for 6 Months or More

The percentage participants with disease stabiliztion for 6 months or more were defined as those treated participants with a best CNS objective response of SD whose disease stabilization lasted 6 months or more from the start of treatment. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

mITT Population

Posted

From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Secondary

Percentage of Participants With a >=20% Volumetric Reduction in CNS Lesions

The percentage of participants with a >=20% volumetric reduction in CNS lesions was defined as the percentage of treated participants achieving at least a 20% volumetric reduction in CNS lesions relative to baseline. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

mITT Population

Posted

Baseline; from the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
OG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00011 affected13 at risk EG0018 affected9 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected13 at risk EG0015 affected9 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected13 at risk EG0012 affected9 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0012 affected9 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected13 at risk EG0010 affected9 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0010 affected9 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Cheilitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0008 affected13 at risk EG0015 affected9 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0005 affected13 at risk EG0010 affected9 at risk
Mucosal inflammation	General disorders	MedDRA	Systematic Assessment	EG0004 affected13 at risk EG0010 affected9 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Oedema	General disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Chills	General disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Facial pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Influenza like illness	General disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0006 affected13 at risk EG0013 affected9 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected13 at risk EG0012 affected9 at risk
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0010 affected9 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Balance disorder	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Hemiparesis	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Memory impairment	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Muscle contraction involuntary	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Paraesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Palmar-Plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0008 affected13 at risk EG0011 affected9 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0004 affected13 at risk EG0012 affected9 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0005 affected13 at risk EG0011 affected9 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0012 affected9 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0010 affected9 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0010 affected9 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Skin chapped	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Skin infection	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0015 affected9 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0013 affected9 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0013 affected9 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0003 affected13 at risk EG0012 affected9 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0013 affected9 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Haemoglobin decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0012 affected9 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Activated partial thromboplastin time shortened	Investigations	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Alanine aminotransferase	Investigations	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Blood bilirubin	Investigations	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Blood glucose abnormal	Investigations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Blood glucose increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Blood phosphorus decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Protein total abnormal	Investigations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Prothrombin time abnormal	Investigations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Weight increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0011 affected9 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Depressed mood	Psychiatric disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0010 affected9 at risk
Hot flush	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0010 affected9 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0012 affected9 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0010 affected9 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0011 affected9 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0012 affected9 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected13 at risk EG0010 affected9 at risk
Abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Deafness	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Fungal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Lacrimation increased	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Lymphoedema	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Major depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Nasal ulcer	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Oral fungal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Oral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Otitis media	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Paronychia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Pericardial effusion	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Restlessness	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Sinus disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Thrombophlebitis superficial	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Vision blurred	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Visual impairment	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
White blood cell count decreased	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected13 at risk EG0011 affected9 at risk
Disorientation	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk
Dry eyes	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected13 at risk EG0010 affected9 at risk

ID	Term
D001943	Breast Neoplasms
D001932	Brain Neoplasms

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D016543	Central Nervous System Neoplasms
D009423	Nervous System Neoplasms
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Term
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D005472	Fluorouracil
D014498	Uracil
D011744	Pyrimidinones
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D002166	Camptothecin
D000470	Alkaloids
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

ID	Title	Description
BG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.
BG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.			6	13	13	13
EG001	Lapatinib Plus Topotecan	Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.			5	9	9	9