Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capec... | NCT00820222

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Lapatinib plus capecitabine	Experimental	Lapatinib 1250 mg once daily and capecitabine 2000mg/m2/day, days 1-14, every 21 days	Drug: capecitabine Drug: lapatinib
Trastuzumab plus capecitabine	Active Comparator	trastuzumab loading dose of 8mg/kg followed by 6mg/kg q3weekly infusions, and capecitabine 2500mg/m2/day, days 1-14, every 21 days	Drug: capecitabine Drug: trastuzumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
capecitabine	Drug	oral medication; daily dose divided into morning and evening dose and taken for 14 days of 21 day cycle	Lapatinib plus capecitabine Trastuzumab plus capecitabine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Central Nervous System (CNS) Metastases (as Assessed by Independent Review) as the Site of First Relapse	CNS relapse is defined as the appearance of >=1 enhancing lesion measuring >=6 millimeters (mm) on T1Weighted (T1W) Magnetic Resonance Imaging (MRI) without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease (defined as the dissemination of cancer throughout the spinal fluid), with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a <6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.	From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

Secondary Outcomes

Measure	Description	Time Frame
Progression Free Survival (PFS), as Assessed by the Investigator	PFS is defined as the interval between the date of randomization and the earliest date of progressive disease (PD), or death due to any cause. PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions based on investigator assessment of both CNS and non-CNS for response.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Females at least 18 years old;
ECOG Performance Status 0-2;
Histologically or cytologically confirmed HER2-positive invasive breast cancer, with Stage IV disease;
Prior treatment with taxanes or anthracyclines is required;
Prior treatment with other chemotherapeutic agents, trastuzumab, endocrine and radiation therapy is permitted;
Baseline LVEF ≥ 50% and not lower than the institutional lower limit of normal;
Concurrent treatment with bisphosphonates is permitted, however treatment must be initiated prior to the first dose of study therapy;
Able to swallow and retain oral medications;
Women with potential to have children must be willing to practice acceptable methods of birth control during the study;
Normal organ and marrow function.

Exclusion Criteria:

History and/or current evidence of CNS metastases. Baseline MRI scan by Independent Reviewer to confirm no brain mets;
Concurrent treatment with an investigational agent or participation in another treatment clinical trial;
Prior therapy with lapatinib or an ErbB2 inhibitor other than trastuzumab (including but not limited to trastuzumab-DM1 and neratinib) and capecitabine;
Known DPD deficiency;
Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormonal therapy for treatment of cancer;
History of allergic reactions attributed to compounds chemically related to lapatinib (quinazolines), capecitabine, fluorouracil or any excipients;
Concomitant use of CYP3A4 inhibitors or inducers;
Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel;
History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast and other known contraindication to MRI;
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 patient's safety or compliance to study procedures;
have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease);
Any on-going toxicity from prior anti cancer therapy except alopecia;
Active cardiac disease;
Uncontrolled infection;
History of other malignancy, unless curatively treated with no evidence of disease for at least 5 years, subjects with adequately treated DCIS or LCIS, adequately treated non-melanoma skin cancer or curatively treated in-situ cancer of the cervix are eligible;
Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of protocol treatment;
Pregnant or lactating females.

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Goodyear	Arizona	85338	United States
Novartis Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25605838	Derived	Pivot X, Manikhas A, Zurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A Phase III, Randomized, Open-Label Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. doi: 10.1200/JCO.2014.57.1794. Epub 2015 Jan 20.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
BG001	Trastuzumab Plus Capecitabine	Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
BG002	Total	Total of all reporting groups

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 Central Nervous System (CNS) Metastases (as Assessed by Independent Review) as the Site of First Relapse

CNS relapse is defined as the appearance of >=1 enhancing lesion measuring >=6 millimeters (mm) on T1Weighted (T1W) Magnetic Resonance Imaging (MRI) without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease (defined as the dissemination of cancer throughout the spinal fluid), with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a <6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.

Modified Intent-to-Treat (M-ITT) Population: all participants who were randomized to study treatment regardless of whether or not treatment was administered and who had no Baseline CNS metastases per Independent Review Committee (IRC) assessment

Posted

Number

participants

From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
OG001	Trastuzumab Plus Capecitabine	Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Units	Counts
Participants	OG000251 OG001250

Title

Denominators

Categories

Title	Measurements
	OG0008 OG00112

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 OG001		Odds Ratio		0.360		Odds Ratio (OR)	0.65			2-Sided	95	0.26	1.63			The Odds Ratio is based on a logistic regression model. The P-value for the test of Odds Ratio is 1.		Superiority or Other

Secondary

Progression Free Survival (PFS), as Assessed by the Investigator

PFS is defined as the interval between the date of randomization and the earliest date of progressive disease (PD), or death due to any cause. PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions based on investigator assessment of both CNS and non-CNS for response.

Intent-to-Treat (ITT) Population: all participants who were randomized to study treatment regardless of whether or not treatment was administered

Posted

Median

95% Confidence Interval

months

From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
OG001	Trastuzumab Plus Capecitabine	Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Secondary

Time to First CNS Progression, Defined as the Time From Randomization Until the Date of Documented CNS Progression as the First Site of Relapse

CNS relapse is defined as the appearance of >=1 enhancing lesion measuring >=6 mm on T1W MRI without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease (defined as the dissemination of cancer throughout the spinal fluid), with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a <6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.

M-ITT Population. Only those participants who had no Baseline CNS metastases and who had CNS progression by radiographic confirmation (per Response Evaluation Criteria in Solid Tumors, 1.0: a 20% increase in the sum of the longest diameter [LD] of target lesions or the appearance of >=1 new lesions) were included in this analysis.

Posted

Mean

Standard Deviation

months

From randomization until the date of documented CNS progression (average of 10 months). Cut-off 11-Jun-2012

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Secondary

Overall Survival

Overall survival is defined as the time from randomization until death due to any cause or to the date of censor. In the absence of confirmation of death, survival time was to be censored at the time of the last investigator contact.

ITT Population

Posted

Median

95% Confidence Interval

months

From randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
OG001	Trastuzumab Plus Capecitabine	Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Secondary

Number of Participants With Overall Response (OR), as Assessed by the Investigator

OR is defined as the number of participants with either a confirmed complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD). CR and PR were assessed per Response Evaluation Criteria in Solid Tumors (RECIST). To be assigned a status of PR or CR, a confirmatory disease assessment was to be performed 28 days (4 weeks) or greater after the criteria for response were first met. In addition, a bone scan must have been obtained to rule out the presence of new bone lesions or progression of existing bone lesions, even if the participant had no bone lesions present at Baseline. If a bone scan was performed at the time of initial response or near the time of response, the bone scan did not need to be repeated.

ITT Population. Only those participants enrolled under protocol amendment 3 were required to have PR or CR confirmation. Those participants enrolled under protocol amendments 1 and 2 were considered to have a "confirmed" response at the time of the first PR or CR regardless of follow-up scans.

Posted

Count of Participants

Participants

From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Secondary

Number of Participants With Clinical Benefit (CB)

CB is defined as the number of participants with evidence of confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD) at any time or stable disease (SD, neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD [defined as at least a 20% increase in the sum of the LD of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions] based on investigator assessment), for at least 24 weeks.

Posted

Count of Participants

Participants

From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Secondary

Duration of Response

Duration of response is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD) until the first documented sign of PD (at least a 20% increase in the sum of the LD of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions) or death due to breast cancer. In the absence of confirmation of death, survival time was to be censored at the time of the last investigator contact.

ITT Population. Only those participants with CR or PR showing PD or death due to breast cancer were analyzed.

Posted

Median

95% Confidence Interval

months

From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 10 months). Cut-off 11-Jun-2012

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
OG001	Trastuzumab Plus Capecitabine

Secondary

Number of Participants With CNS Progression at Any Time

CNS progression was documented by a brain scan and was indicated by the investigator on the follow-up electronic Case Report Form. CNS relapse is defined as the appearance of >=1 enhancing lesion measuring >=6 mm on T1W MRI without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease, with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a <6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.

M-ITT Population

Posted

Number

participants

From the time of randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Secondary

Number of Participants With Qualitative and Quantitative Toxicities

Qualitative and quantitative toxicities were measured as AEs. See the outcome measure entitled "Number of participants with the indicated Grade 3 or Grade 4 Adverse Events (AEs) occurring in >=2 participants in either treatment arm" and the AE module of this results summary for a list of AEs occurring in the study. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Safety Population

Posted

From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months)

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
OG001	Trastuzumab Plus Capecitabine	Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Secondary

Number of Participants Expressing Glucocorticoid Receptor, Phosphatase and Tensin Homolog (PTEN), Phosphatidylinositide 3-kinase (PI3K)/AKT, Protein 53 (P53), Insulin-like Growth Factor-1 (IGF-1), and Genes Involved in Cell Cycle Regulation

Because the study terminated early, pharmacogenetic and biomarker analyses were not performed.

ITT Population

Posted

Baseline

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
OG001	Trastuzumab Plus Capecitabine	Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Secondary

Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was related to study drug. AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE.

Safety Population: all participants in the ITT Population who received at least one dose of investigational product, based on the actual treatment received if this differed from that to which the participant was randomized

Posted

Count of Participants

Participants

From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months).

ID	Title	Description
OG000	Lapatinib Plus Capecitabine	Participants received a daily dose of 5 tablets of lapatinib (1250 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/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

Arm/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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	12	270	41	270	241	270
EG001	Trastuzumab Plus Capecitabine	Participants received an intravenous (IV) infusion of trastuzumab 8 mg/kilogram (kg) on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 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 food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	3	267	51	267	236	267

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0011 affected267 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (20.1)	Systematic Assessment	EG0002 affected270 at risk EG0016 affected267 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0012 affected267 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0011 affected267 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Colitis	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Constipation	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG0002 affected270 at risk EG0010 affected267 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG0004 affected270 at risk EG00110 affected267 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Gastrointestinal inflammation	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Nausea	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0012 affected267 at risk
Vomiting	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG0002 affected270 at risk EG0012 affected267 at risk
Asthenia	General disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Chest pain	General disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0011 affected267 at risk
General physical health deterioration	General disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Mucosal inflammation	General disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Non-cardiac chest pain	General disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0012 affected267 at risk
Pain	General disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Pyrexia	General disorders	MedDRA (20.1)	Systematic Assessment	EG0003 affected270 at risk EG0013 affected267 at risk
Biliary colic	Hepatobiliary disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Bronchitis	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Cellulitis	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0011 affected267 at risk
Clostridium difficile infection	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Device related infection	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Erysipelas	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0011 affected267 at risk
Gastroenteritis	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0011 affected267 at risk
Gastroenteritis bacterial	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Infection	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Localised infection	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Pharyngitis	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Pneumonia	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0002 affected270 at risk EG0012 affected267 at risk
Pyelonephritis acute	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Sepsis	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0011 affected267 at risk
Septic shock	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0012 affected267 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Urinary tract infection	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0012 affected267 at risk
Viral infection	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Viral pharyngitis	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Wound infection	Infections and infestations	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Alanine aminotransferase increased	Investigations	MedDRA (20.1)	Systematic Assessment	EG0002 affected270 at risk EG0011 affected267 at risk
Blood bilirubin increased	Investigations	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0011 affected267 at risk
Ejection fraction decreased	Investigations	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0013 affected267 at risk
Platelet count decreased	Investigations	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (20.1)	Systematic Assessment	EG0002 affected270 at risk EG0010 affected267 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0013 affected267 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Cerebral haematoma	Nervous system disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Headache	Nervous system disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Hemiplegia	Nervous system disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Neurological decompensation	Nervous system disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Dysuria	Renal and urinary disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Cervical dysplasia	Reproductive system and breast disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG0002 affected270 at risk EG0010 affected267 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG0003 affected270 at risk EG0016 affected267 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0012 affected267 at risk
Pelvic venous thrombosis	Vascular disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0010 affected267 at risk
Thrombophlebitis	Vascular disorders	MedDRA (20.1)	Systematic Assessment	EG0001 affected270 at risk EG0012 affected267 at risk
Thrombosis	Vascular disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0012 affected267 at risk
Vena cava thrombosis	Vascular disorders	MedDRA (20.1)	Systematic Assessment	EG0000 affected270 at risk EG0011 affected267 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (20.1)	Systematic Assessment	EG00022 affected270 at risk EG00127 affected267 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (20.1)	Systematic Assessment	EG00011 affected270 at risk EG00121 affected267 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (20.1)	Systematic Assessment	EG00038 affected270 at risk EG00144 affected267 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG00021 affected270 at risk EG00116 affected267 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG000125 affected270 at risk EG001107 affected267 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG00021 affected270 at risk EG00119 affected267 at risk
Nausea	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG00082 affected270 at risk EG00150 affected267 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG00016 affected270 at risk EG00123 affected267 at risk
Vomiting	Gastrointestinal disorders	MedDRA (20.1)	Systematic Assessment	EG00035 affected270 at risk EG00127 affected267 at risk
Asthenia	General disorders	MedDRA (20.1)	Systematic Assessment	EG00046 affected270 at risk EG00145 affected267 at risk
Fatigue	General disorders	MedDRA (20.1)	Systematic Assessment	EG00026 affected270 at risk EG00133 affected267 at risk
Mucosal inflammation	General disorders	MedDRA (20.1)	Systematic Assessment	EG00021 affected270 at risk EG00127 affected267 at risk
Pyrexia	General disorders	MedDRA (20.1)	Systematic Assessment	EG00019 affected270 at risk EG00125 affected267 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (20.1)	Systematic Assessment	EG00035 affected270 at risk EG00126 affected267 at risk
Alanine aminotransferase increased	Investigations	MedDRA (20.1)	Systematic Assessment	EG00034 affected270 at risk EG00135 affected267 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (20.1)	Systematic Assessment	EG00033 affected270 at risk EG00130 affected267 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (20.1)	Systematic Assessment	EG00017 affected270 at risk EG00111 affected267 at risk
Blood bilirubin increased	Investigations	MedDRA (20.1)	Systematic Assessment	EG00019 affected270 at risk EG0019 affected267 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (20.1)	Systematic Assessment	EG00028 affected270 at risk EG00121 affected267 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Systematic Assessment	EG00016 affected270 at risk EG00113 affected267 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Systematic Assessment	EG00014 affected270 at risk EG0019 affected267 at risk
Headache	Nervous system disorders	MedDRA (20.1)	Systematic Assessment	EG00015 affected270 at risk EG00117 affected267 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG00022 affected270 at risk EG00116 affected267 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Systematic Assessment	EG00011 affected270 at risk EG00118 affected267 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Systematic Assessment	EG00015 affected270 at risk EG0017 affected267 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Systematic Assessment	EG00021 affected270 at risk EG00113 affected267 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Systematic Assessment	EG000142 affected270 at risk EG001160 affected267 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Systematic Assessment	EG00066 affected270 at risk EG00121 affected267 at risk

Ancestor Terms

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
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Term
D001932	Brain Neoplasms
D001943	Breast Neoplasms

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

ID	Term
D000069287	Capecitabine
D000077341	Lapatinib
D000068878	Trastuzumab