LOGiC - Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib

• ClinicalTrials.gov Identifier: NCT00680901
• Recruitment Status: Active, not recruiting
• First Posted: May 20, 2008
• Results First Posted: October 29, 2013
• Last Update Posted: April 3, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Neoplasms, Gastrointestinal Tract
• Interventions: Drug: Lapatinib; Drug: Placebo; Drug: Capecitabine; Drug: Oxaliplatin
• Enrollment: 545

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Period Title: Overall Study
Started	272	273
Ongoing: On Study Treatment	16	13
Ongoing: In Follow Up	45	41
Completed	199	197
Not Completed	73	76
Reason Not Completed
Lost to Follow-up	8	8
Withdrawal by Subject	4	13
Physician Decision	0	1
Ongoing: On Study Treatment	16	13
Ongoing: In Follow Up	45	41

Baseline Characteristics

Arm/Group Title		CapeOx + Lapatinib	CapeOx + Placebo	Total
Arm/Group Description		Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Total of all reporting groups
Overall Number of Baseline Participants		272	273	545
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	272 participants	273 participants	545 participants
		59.4 (11.20)	58.5 (11.23)	58.9 (11.21)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	272 participants	273 participants	545 participants
	Female	66 24.3%	73 26.7%	139 25.5%
	Male	206 75.7%	200 73.3%	406 74.5%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	272 participants	273 participants	545 participants
African American/African Heritage (Hrtg)		2	3	5
American Indian or Alaska Native		3	3	6
Central/South Asian Hrtg		11	3	14
Japanese/East Asian Hrtg/South East Asian Hrtg		112	114	226
White		144	150	294

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall Survival is defined as the time from randomization until death due to any cause. Participants who had not died were censored at the follow-up visit as either follow-up ended or follow-up ongoing.
Time Frame	From randomization until death due to any cause (average of 51 weeks)

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population: all randomized participants with Human Epidermal Growth Factor Receptor 2 (ErbB2)-positive tumors (based on Fluorescence In Situ Hybridization [FISH]-positive designated central laboratory assessment).

Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed	249	238
Median (95% Confidence Interval); Unit of Measure: months
	12.2; (10.6 to 14.2)	10.5; (9.0 to 11.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CapeOx + Lapatinib, CapeOx + Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3492
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified log-rank test was conducted stratifying for prior adjuvant/neo-adjuvant treatment use and region.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.12
	Estimation Comments	Pike estimator of HR was based on the stratified log rank test.

2. Primary Outcome

Title	Overall Survival in All Randomized Participants
Description	Overall Survival is defined as the time from randomization until death due to any cause. Participants who had not died were censored at the follow-up visit as either follow-up ended or follow-up ongoing.
Time Frame	From randomization until death due to any cause (average of 51 weeks)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants randomized to study treatment, regardless of whether they actually received study medication.

Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed	272	273
Median (95% Confidence Interval); Unit of Measure: months
	11.9; (10.4 to 13.8)	10.4; (9.1 to 11.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CapeOx + Lapatinib, CapeOx + Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3244
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified log-rank test was conducted stratifying for prior adjuvant/neo-adjuvant treatment use and region.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.10
	Estimation Comments	Pike estimator of HR was based on the stratified log rank test.

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS is defined as the interval between the date of randomization and the earliest date of disease progression (PD) or death due to any cause. Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started or the appearance of >= 1 new lesion. Participants who did not have a radiological assessed PD but had symptomatic PD were also counted. Participants who had neither progressed nor died were censored at the follow-up visit as either follow-up ended or follow-up ongoing. Participants who received non-study anti-cancer therapies before disease progression were treated as censored.
Time Frame	From randomization until the earliest date of disease progression or death due to any cause (average of 30 weeks)

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population

Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed	249	238
Median (95% Confidence Interval); Unit of Measure: months
	6.0; (5.6 to 7.0)	5.4; (4.4 to 5.7)

4. Secondary Outcome

Title	Number of Participants With a Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR)
Description	A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target and non-target lesions) or a PR (at least a 30% decrease in the sum of the longest diameters [LD] of target lesions, taking as a reference the Baseline sum LD) as assessed by the investigator (confirmed by radiographic imaging within 4 weeks from initial observations).
Time Frame	From randomization until the date of the first documented response of CR or PR (average of 9 weeks)

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population

Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed	249	238
Measure Type: Number; Unit of Measure: Participants
	131	93

5. Secondary Outcome

Title	Number of Participants With Clinical Benefit (CB)
Description	CB is defined as evidence of a CR (disappearance of all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD) at any time or stable disease (SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started) as assessed by the investigator.
Time Frame	From randomization until disease progression (PD) or death due to any cause (average of 30 weeks)

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population

Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed	249	238
Measure Type: Number; Unit of Measure: Participants
	199	188

6. Secondary Outcome

Title	Time to Response (TTR)
Description	TTR is defined as the time from randomization until the date of the first documented evidence of CR (the disappearance if all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking a reference the Baseline sum LD) as assessed by the investigator.
Time Frame	From Baseline (Day 1) until the first documented evidence of confirmed CR or PR (average of 9 weeks)

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population. Only those participants who had a confirmed CR or PR were analyzed for duration of response.

Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed	131	93
Median (95% Confidence Interval); Unit of Measure: Months
	1.4; (1.4 to 1.5)	1.4; (1.4 to 1.5)

7. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR is defined as the time from the first documented evidence of a CR (the disappearance of all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD) until the first documented sign of PD or death due to any cause. Per RECIST, PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started or the appearance of >=1 new lesion. Participants who had neither progressed nor died were censored at the follow-up visit as either follow-up ended or follow-up ongoing. Participants who received non-study anti-cancer therapies before disease progression were treated as censored.
Time Frame	From the time of the first documented evidence of a confirmed CR or PR until the earliest date of disease progression or death due to any cause (average of 36 weeks)

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population. Only those participants who had a confirmed CR or PR were analyzed for duration of response.

Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed	131	93
Median (95% Confidence Interval); Unit of Measure: Months
	7.3; (6.4 to 8.5)	5.6; (4.6 to 6.0)

8. Secondary Outcome

Title	Number of Participants With Any Non-serious Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) or Any Serious Adverse Event (SAE)
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Time Frame	From the first dose of study medication until 30 days after the last dose (average of 229 days)

Outcome Measure Data

Analysis Population Description

Safety Population: all randomized participants who received at least one dose of study medication

Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed	270	267
Measure Type: Number; Unit of Measure: Participants
Non-serious AEs	245	216
SAEs	72	52

9. Secondary Outcome

Title	Number of Participants With Adverse Events of the Indicated Severity, Per the National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE)
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. AE/SAE severity was graded according to NCI CTCAE, version 3.0: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.
Time Frame	From the first dose of study medication until 30 days after the last dose (average of 229 days)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed	270	267
Measure Type: Number; Unit of Measure: Participants
Grade 1	44	57
Grade 2	88	76
Grade 3	91	69
Grade 4	17	25
Grade 5	15	9

10. Secondary Outcome

Title	Mean Change in Scores on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) From Baseline to Week 36
Description	The QLQ-C30, a self administered tool used to assess HROL, consists of 30 items that assesses 15 domains consisting of 5 functional scales (s.) (physical, role, emotional, cognitive, social) and nine symptom s. or single items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status or QOL s.. For the functional s. and symptom s. or single items, participants assessed using a 4-point s. (1=not at all; 2=a little; 3=quite a bit; 4=very much), whereas global health status or QOL was assessed using a 7-item Likert s., ranging from "poor" to "excellent." All s. and single-item scores ranged from 0 to 100. For the functional scores, a higher score indicated a better HRQOL, i.e. 0=worst HRQOL, 100=best HRQOL; for the symptom s. or single items , a higher score indicated a high level of symptoms and problems, i.e. 0=no symptoms, 100=most severe symptoms.
Time Frame	From Baseline (Day1) to Week 36

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population. Only those participants contributing data at the indicated time point were analyzed.

Arm/Group Title		CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:		Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed		50	19
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Global health status/quality of life, n= 49, 19	Number Analyzed	49 participants	19 participants
		6.6 (20.97)	1.8 (17.25)
Physical functioning, n=50, 19	Number Analyzed	50 participants	19 participants
		0.6 (13.46)	-4.4 (19.19)
Role functioning, n=50, 19	Number Analyzed	50 participants	19 participants
		4.7 (21.31)	-1.8 (25.39)
Emotional functioning, n=50, 19	Number Analyzed	50 participants	19 participants
		4.1 (18.91)	0.4 (24.29)
Cognitive functioning, n=50, 19	Number Analyzed	50 participants	19 participants
		-0.2 (16.02)	-5.3 (15.77)
Social functioning, n=50, 19	Number Analyzed	50 participants	19 participants
		6.7 (25.64)	-4.4 (38.43)
Fatigue symptom scale, n=50, 19	Number Analyzed	50 participants	19 participants
		-6.0 (19.08)	2.3 (24.45)
Nausea and vomiting symptom scale, n=50, 19	Number Analyzed	50 participants	19 participants
		-4.7 (13.90)	6.1 (14.92)
Pain symptom scale, n=50, 19	Number Analyzed	50 participants	19 participants
		-6.7 (21.56)	0.0 (34.69)
Dyspnea symptom scale, n=50, 18	Number Analyzed	50 participants	18 participants
		0.7 (21.81)	5.6 (28.58)
Insomnia symptom scale, n=50, 19	Number Analyzed	50 participants	19 participants
		-4.0 (21.97)	-1.8 (30.38)
Appetite loss symptom scale, n=50, 19	Number Analyzed	50 participants	19 participants
		-8.0 (28.22)	-5.3 (31.94)
Constipation symptom scale, n=49, 19	Number Analyzed	49 participants	19 participants
		-6.8 (20.39)	0.0 (41.57)
Diarrhea symptom scale, n=50, 19	Number Analyzed	50 participants	19 participants
		6.0 (26.68)	1.8 (13.49)

11. Secondary Outcome

Title	Mean Change in Scores on the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) From Baseline to Week 36
Description	The EORTC QLQ-STO22, the Gastric module of QLQ-C30, is a self administered tool use to assess HROOL of patients with gastric cancer. It consists of 22 items consisting of nine symptom scales or single items (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, taste, body image, hair loss) that were developed for participants with gastric cancer. For the symptom scales or single items, participants assessed using a 4-point scale (1=not at all; 2=a little; 3=quite a bit; 4=very much). All scales and single-item scores ranged from 0 to 100. For the symptom scales or single items, a higher score indicated a high level of symptoms and problems, i.e. 0=no symptoms, 100=most severe symptoms.
Time Frame	From Baseline (Day1) to Week 36

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population. Only those participants contributing data at the indicated time point were analyzed.

Arm/Group Title		CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:		Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed		48	16
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Dysphagia symptom scale, n=48, 15	Number Analyzed	48 participants	15 participants
		-6.7 (14.81)	1.4 (19.40)
Pain symptom scale, n=26, 15	Number Analyzed	26 participants	15 participants
		-12.6 (17.01)	-4.0 (17.63)
Reflux symptom scale, n=48, 16	Number Analyzed	48 participants	16 participants
		-8.3 (16.80)	4.2 (25.94)
Eating restrictions symptom scale, n=48, 16	Number Analyzed	48 participants	16 participants
		-7.8 (17.65)	0.3 (23.28)
Anxiety symptom scale, n=48, 16	Number Analyzed	48 participants	16 participants
		-16.7 (24.04)	-7.3 (22.65)
Dry mouth symptom scale, n=46, 16	Number Analyzed	46 participants	16 participants
		-8.0 (33.84)	8.3 (31.03)
Taste symptom scale, n=48, 16	Number Analyzed	48 participants	16 participants
		-3.5 (25.02)	4.2 (16.67)
Body image symptom scale, n=48, 16	Number Analyzed	48 participants	16 participants
		-10.4 (25.87)	-2.1 (28.46)
Hair loss symptom scale, n=2, 0	Number Analyzed	2 participants	0 participants
		-16.7 (23.57)

12. Secondary Outcome

Title	Mean Change in Scores on the Questionnaire EuroQoL-5 Dimensions (EQ-5D) From Baseline to Week 36
Description	The EQ-5D is a generic preference-based HROOL self administered tool comprising of a 5-dimensional health status measure (5D utility measure) and a visual analog rating scale feeling thermometer (T.). 5D utility measures mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. T. assesses participant's current health state. Each 5D utility question was responded to on a 3-point scale, indicating the level of impairment (1=no problem; 2=some or moderate problem(s); 3=unable, or extreme problems). The index utility values corresponding to the 243 health states were defined by the EuroQol classification and calculated based on country-specific regression coefficients. In the UK-based value set, the possible EQ-5D index utility values range from -0.594 to 1. The T. value ranges from 0 to 100. EQ-5D utility index score 0=death, 1=perfect health, -0.594 = worse than death. The T. score: 100=best imaginable health state, 0=worse imaginable health state.
Time Frame	From Baseline (Day1) to Week 36

Outcome Measure Data

Analysis Population Description

Primary Efficacy Population. Only those participants contributing data at the indicated time point were analyzed.

Arm/Group Title		CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:		Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed		50	20
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Utility Index, n=50, 19	Number Analyzed	50 participants	19 participants
		0.1 (0.25)	-0.1 (0.22)
Thermometer, n=50, 20	Number Analyzed	50 participants	20 participants
		5.5 (12.76)	2.6 (14.01)

13. Secondary Outcome

Title	Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Clinical Chemistry Parameters
Description	Data are summarized by NCI CTCAE, version 3.0 toxicity grades. Data are reported as the number of participants who had a Grade 3 (G3) or Grade 4 (G4) toxicity for the indicated clinical chemistry parameters: G3 indicates a severe toxicity, and G4 indicates a life-threatening toxicity. Clinical chemistry parameters included: Albumin, Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amino Transeferase (AST), Total Bilirubin (TB), Calcium (Hypercalcemia and Hypocalcemia), Creatine Kinase (CK), Creatinine, Glucose (Hyperglycemia [high] and Hypoglycemia [low]), Potassium (Hyperkalemia [high] and Hypokalemia [low]), Magnesium (Hypermagnesemia [high] and Hypomagnesemia [low]), and Sodium (Hypernatremia [high] and Hyponatremia [low]).
Time Frame	From Baseline (Day 1) until 28 days after the last dose (average of 239 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Different participants may have been assessed for different parameters; thus the number of participants analyzed reflects everyone in the Safety Population. The number of participants assessed for each parameter is indicated by "n=X, X".

Arm/Group Title		CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:		Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed		270	267
Measure Type: Number; Unit of Measure: Participants
Albumin, G3, n=257, 258	Number Analyzed	257 participants	258 participants
		3	4
Albumin, G4, n=257, 258	Number Analyzed	257 participants	258 participants
		0	0
AP, G3, n=260, 260	Number Analyzed	260 participants	260 participants
		5	12
AP, G4, n=260, 260	Number Analyzed	260 participants	260 participants
		0	0
ALT, G3, n=260, 262	Number Analyzed	260 participants	262 participants
		2	4
ALT, G4, n=260, 262	Number Analyzed	260 participants	262 participants
		0	0
AST, G3, n=260, 262	Number Analyzed	260 participants	262 participants
		2	6
AST, G4, n=260, 262	Number Analyzed	260 participants	262 participants
		0	0
TB, G3, n=260, 261	Number Analyzed	260 participants	261 participants
		6	3
TB, G4, n=260, 261	Number Analyzed	260 participants	261 participants
		2	5
Calcium (Hypercalcemia), G3, n=256, 262	Number Analyzed	256 participants	262 participants
		0	0
Calcium (Hypercalcemia), G4, n=256, 262	Number Analyzed	256 participants	262 participants
		0	0
Calcium (Hypocalcemia), G3, n=256, 262	Number Analyzed	256 participants	262 participants
		3	4
Calcium (Hypocalcemia), G4, n=256, 262	Number Analyzed	256 participants	262 participants
		0	0
CK, G3, n=1, 3	Number Analyzed	1 participants	3 participants
		0	0
CK, G4, n=1, 3	Number Analyzed	1 participants	3 participants
		0	0
Creatinine, G3, n=260, 262	Number Analyzed	260 participants	262 participants
		2	1
Creatinine, G4, n=260, 262	Number Analyzed	260 participants	262 participants
		0	0
Glucose (Hyperglycemia), G3, n=259, 262	Number Analyzed	259 participants	262 participants
		6	8
Glucose (Hyperglycemia), G4, n=259, 262	Number Analyzed	259 participants	262 participants
		1	0
Glucose (Hypoglycemia), G3, n=259, 262	Number Analyzed	259 participants	262 participants
		1	1
Glucose (Hypoglycemia), G4, n=259, 262	Number Analyzed	259 participants	262 participants
		0	2
Potassium (Hyperkalemia), G3, n=259, 261	Number Analyzed	259 participants	261 participants
		2	1
Potassium (Hyperkalemia), G4, n=259, 261	Number Analyzed	259 participants	261 participants
		1	0
Potassium (Hypokalemia), G3, n=259, 261	Number Analyzed	259 participants	261 participants
		21	11
Potassium (Hypokalemia), G4, n=259, 261	Number Analyzed	259 participants	261 participants
		3	1
Magnesium (Hypermagnesemia), G3, n=254, 256	Number Analyzed	254 participants	256 participants
		5	5
Magnesium (Hypermagnesemia), G4, n=254, 256	Number Analyzed	254 participants	256 participants
		0	0
Magnesium (Hypomagnesemia), G3, n=254, 256	Number Analyzed	254 participants	256 participants
		1	0
Magnesium (Hypomagnesemia), G4, n=254, 256	Number Analyzed	254 participants	256 participants
		0	0
Sodium (Hypernatremia), G3, n=259, 261	Number Analyzed	259 participants	261 participants
		1	2
Sodium (Hypernatremia), G4, n=259, 261	Number Analyzed	259 participants	261 participants
		2	0
Sodium (Hyponatremia), G3, n=259, 261	Number Analyzed	259 participants	261 participants
		19	16
Sodium (Hyponatremia), G4, n=259, 261	Number Analyzed	259 participants	261 participants
		2	4

14. Secondary Outcome

Title	Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Hematology Parameters
Description	Data are summarized by NCI CTCAE, version 3.0 toxicity grades. Data are reported as the number of participants who had a Grade 3 (G3) or Grade 4 (G4) toxicity for indicated hematology parameters: G3 indicates a severe toxicity, and G4 indicates a life-threatening toxicity. Hematology parameter included: Hemoglobin (Hemo), Total Neutrophils (TN) Absolute, Platelet Count (PC), and White Blood Cell (WBC) Count.
Time Frame	From Baseline (Day 1) until 28 days after the last dose (average of 239 days)

Outcome Measure Data

Analysis Population Description

Safety Population. Different participants may have been assessed for different parameters; thus the number of participants analyzed reflects everyone in the Safety Population. The number of participants assessed for each parameter is indicated by "n=X, X".

Arm/Group Title		CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description:		Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
Overall Number of Participants Analyzed		270	267
Measure Type: Number; Unit of Measure: Participants
Hemo, G3, n=261, 263	Number Analyzed	261 participants	263 participants
		26	19
Hemo, G4, n=261, 263	Number Analyzed	261 participants	263 participants
		9	8
TN Absolute, G3, n=240, 248	Number Analyzed	240 participants	248 participants
		22	27
TN Absolute, G4, n=240, 248	Number Analyzed	240 participants	248 participants
		6	2
PC, G3, n=261, 261	Number Analyzed	261 participants	261 participants
		21	29
PC, G4, n=261, 261	Number Analyzed	261 participants	261 participants
		5	2
WBC Count, G3, n=261, 262	Number Analyzed	261 participants	262 participants
		12	4
WBC Count, G4, n=261, 262	Number Analyzed	261 participants	262 participants
		1	1

Adverse Events

Time Frame	Serious Adverse Events (SAEs) and non-serious AEs were collected from the first dose of study treatment until 30 days following the last dose of study treatment (average of 229 days).
Adverse Event Reporting Description	SAEs and non-serious AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication, according to the actual treatment recevied.
Arm/Group Title	CapeOx + Lapatinib	CapeOx + Placebo
Arm/Group Description	Participants received oxaliplatin (Ox) 130 milligrams (mg)/ meters squared (m^2) intravenously (IV) on Day 1 of each 21-day cycle plus capecitabine (Cape) 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib 1250 mg orally once a day from Day 1 continuously throughout each cycle, even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.	Participants received oxaliplatin 130 mg/ m^2 IV on Day 1 of each 21-day cycle plus capecitabine 1700 mg/m^2 per day orally divided into two daily doses beginning the evening of Day 1 and ending the morning of Day 15 (28 doses per cycle) followed by a minimum required 6.5 day rest period per cycle. Participants also received lapatinib matching placebo from Day 1 continuously throughout each cycle even during the 6.5 day rest period. Oxaliplatin was administered for a maximum of 8 cycles; after discontinuation of oxliplatin, capecitabine and lapatinib matching placebo were continued until diease progression, unacceptable toxicity, or consent withdrawal. The capecitabine dose could have been escalated to 2000 mg/m^2 per day after the completion of the first cycle at the investigator's discretion.
All-Cause Mortality
	CapeOx + Lapatinib	CapeOx + Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	CapeOx + Lapatinib	CapeOx + Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	72/270 (26.67%)	52/267 (19.48%)
Blood and lymphatic system disorders
Anaemia † 1	6/270 (2.22%)	4/267 (1.50%)
Neutropenia † 1	3/270 (1.11%)	0/267 (0.00%)
Thrombocytopenia † 1	2/270 (0.74%)	1/267 (0.37%)
Cardiac disorders
Atrial fibrillation † 1	2/270 (0.74%)	0/267 (0.00%)
Left ventricular dysfunction † 1	2/270 (0.74%)	0/267 (0.00%)
Acute coronary syndrome † 1	1/270 (0.37%)	0/267 (0.00%)
Acute myocardial infarction † 1	1/270 (0.37%)	0/267 (0.00%)
Cardiac tamponade † 1	1/270 (0.37%)	0/267 (0.00%)
Cardio-respiratory arrest † 1	1/270 (0.37%)	0/267 (0.00%)
Pericardial effusion † 1	0/270 (0.00%)	1/267 (0.37%)
Congenital, familial and genetic disorders
Pyloric stenosis † 1	1/270 (0.37%)	0/267 (0.00%)
Gastrointestinal disorders
Diarrhoea † 1	16/270 (5.93%)	1/267 (0.37%)
Vomiting † 1	7/270 (2.59%)	6/267 (2.25%)
Nausea † 1	6/270 (2.22%)	2/267 (0.75%)
Abdominal pain † 1	2/270 (0.74%)	3/267 (1.12%)
Gastrointestinal haemorrhage † 1	3/270 (1.11%)	2/267 (0.75%)
Dysphagia † 1	2/270 (0.74%)	1/267 (0.37%)
Gastric Haemorrhage † 1	1/270 (0.37%)	2/267 (0.75%)
Abdominal pain upper † 1	1/270 (0.37%)	1/267 (0.37%)
Haematemesis † 1	0/270 (0.00%)	2/267 (0.75%)
Intestinal obstruction † 1	1/270 (0.37%)	1/267 (0.37%)
Melaena † 1	1/270 (0.37%)	1/267 (0.37%)
Small intestinal obstruction † 1	2/270 (0.74%)	0/267 (0.00%)
Upper gastrointestinal haemorrhage † 1	0/270 (0.00%)	2/267 (0.75%)
Enterocutaneous fistula † 1	1/270 (0.37%)	0/267 (0.00%)
Gastric dilatation † 1	0/270 (0.00%)	1/267 (0.37%)
Gastrointestinal obstruction † 1	0/270 (0.00%)	1/267 (0.37%)
Gingival bleeding † 1	1/270 (0.37%)	0/267 (0.00%)
Ileus spastic † 1	0/270 (0.00%)	1/267 (0.37%)
Large intestine perforation † 1	0/270 (0.00%)	1/267 (0.37%)
Mesenteric vein thrombosis † 1	1/270 (0.37%)	0/267 (0.00%)
Obstruction gastric † 1	0/270 (0.00%)	1/267 (0.37%)
General disorders
Ashtenia † 1	2/270 (0.74%)	4/267 (1.50%)
Pyrexia † 1	4/270 (1.48%)	1/267 (0.37%)
Fatigue † 1	3/270 (1.11%)	0/267 (0.00%)
Death † 1	2/270 (0.74%)	0/267 (0.00%)
Condition aggravated † 1	0/270 (0.00%)	1/267 (0.37%)
Device occlusion † 1	0/270 (0.00%)	1/267 (0.37%)
Drowning † 1	0/270 (0.00%)	1/267 (0.37%)
Multi-organ failure † 1	1/270 (0.37%)	0/267 (0.00%)
Oedema peripheral † 1	1/270 (0.37%)	0/267 (0.00%)
Sudden death † 1	1/270 (0.37%)	0/267 (0.00%)
Hepatobiliary disorders
Jaundice † 1	1/270 (0.37%)	0/267 (0.00%)
Jaundice cholestatic † 1	0/270 (0.00%)	1/267 (0.37%)
Immune system disorders
Drug hypersensitivity † 1	1/270 (0.37%)	0/267 (0.00%)
Hypersensitivity † 1	1/270 (0.37%)	0/267 (0.00%)
Infections and infestations
Pneumonia † 1	5/270 (1.85%)	3/267 (1.12%)
Sepsis † 1	1/270 (0.37%)	1/267 (0.37%)
Abdominal infection † 1	1/270 (0.37%)	0/267 (0.00%)
Bacteraemia † 1	1/270 (0.37%)	0/267 (0.00%)
Cellulitis † 1	0/270 (0.00%)	1/267 (0.37%)
Enteritis infectious † 1	0/270 (0.00%)	1/267 (0.37%)
Enterocolitis infectious † 1	0/270 (0.00%)	1/267 (0.37%)
Gastroenteritis † 1	1/270 (0.37%)	0/267 (0.00%)
Herpes zoster † 1	0/270 (0.00%)	1/267 (0.37%)
Lung abscess † 1	0/270 (0.00%)	1/267 (0.37%)
Peritonitis † 1	0/270 (0.00%)	1/267 (0.37%)
Upper respiratory tract infection † 1	0/270 (0.00%)	1/267 (0.37%)
Injury, poisoning and procedural complications
Face injury † 1	0/270 (0.00%)	1/267 (0.37%)
Femure fracture † 1	0/270 (0.00%)	1/267 (0.37%)
Spinal cord injury thoracic † 1	0/270 (0.00%)	1/267 (0.37%)
Investigations
Ejection fraction decreased † 1	1/270 (0.37%)	1/267 (0.37%)
Alanine aminotransferase increased † 1	0/270 (0.00%)	1/267 (0.37%)
Blood bilirubin increased † 1	0/270 (0.00%)	1/267 (0.37%)
Haemoglobin decreased † 1	1/270 (0.37%)	0/267 (0.00%)
Liver function test abnormal † 1	0/270 (0.00%)	1/267 (0.37%)
Platelet count decreased † 1	1/270 (0.37%)	0/267 (0.00%)
Weight decreased † 1	0/270 (0.00%)	1/267 (0.37%)
Metabolism and nutrition disorders
Decreased appetite † 1	4/270 (1.48%)	3/267 (1.12%)
Dehydration † 1	6/270 (2.22%)	1/267 (0.37%)
Hypokalaemia † 1	2/270 (0.74%)	1/267 (0.37%)
Hyponatraemia † 1	2/270 (0.74%)	0/267 (0.00%)
Hyperglycaemia † 1	1/270 (0.37%)	0/267 (0.00%)
Hyperkalaemia † 1	1/270 (0.37%)	0/267 (0.00%)
Musculoskeletal and connective tissue disorders
Arhtralgia † 1	0/270 (0.00%)	1/267 (0.37%)
Bone pain † 1	0/270 (0.00%)	1/267 (0.37%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage † 1	1/270 (0.37%)	0/267 (0.00%)
Nervous system disorders
Aphasia † 1	1/270 (0.37%)	0/267 (0.00%)
Cerebrovascular accident † 1	1/270 (0.37%)	0/267 (0.00%)
Convulsion † 1	0/270 (0.00%)	1/267 (0.37%)
Dizziness † 1	1/270 (0.37%)	0/267 (0.00%)
Epilepsy † 1	1/270 (0.37%)	0/267 (0.00%)
Haemorrhage intracranial † 1	0/270 (0.00%)	1/267 (0.37%)
Nervous system disorder † 1	1/270 (0.37%)	0/267 (0.00%)
Paraesthesia † 1	1/270 (0.37%)	0/267 (0.00%)
Speech disorder † 1	1/270 (0.37%)	0/267 (0.00%)
Syncope † 1	0/270 (0.00%)	1/267 (0.37%)
Psychiatric disorders
Confusional state † 1	0/270 (0.00%)	1/267 (0.37%)
Renal and urinary disorders
Renal failure acute † 1	1/270 (0.37%)	1/267 (0.37%)
Oliguria † 1	1/270 (0.37%)	0/267 (0.00%)
Renal failure † 1	1/270 (0.37%)	0/267 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	3/270 (1.11%)	2/267 (0.75%)
Pneumonia aspiration † 1	2/270 (0.74%)	0/267 (0.00%)
Bronchospasm † 1	0/270 (0.00%)	1/267 (0.37%)
Pharyngeal haemorrhage † 1	0/270 (0.00%)	1/267 (0.37%)
Pulmonary infarction † 1	1/270 (0.37%)	0/267 (0.00%)
Vascular disorders
Circulatory collapse † 1	1/270 (0.37%)	0/267 (0.00%)
Deep vein thrombosis † 1	1/270 (0.37%)	0/267 (0.00%)
Haemorrhage † 1	1/270 (0.37%)	0/267 (0.00%)
Venous thrombosis † 1	1/270 (0.37%)	0/267 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	CapeOx + Lapatinib	CapeOx + Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	245/270 (90.74%)	216/267 (80.90%)
Gastrointestinal disorders
Nausea † 1	128/270 (47.41%)	113/267 (42.32%)
Diarrhoea † 1	146/270 (54.07%)	76/267 (28.46%)
Vomiting † 1	115/270 (42.59%)	93/267 (34.83%)
Constipation † 1	30/270 (11.11%)	52/267 (19.48%)
Abdominal pain † 1	26/270 (9.63%)	31/267 (11.61%)
Abdominal pain upper † 1	18/270 (6.67%)	27/267 (10.11%)
Dyspepsia † 1	13/270 (4.81%)	19/267 (7.12%)
Stomatitis † 1	19/270 (7.04%)	10/267 (3.75%)
Abdominal distension † 1	16/270 (5.93%)	8/267 (3.00%)
Dysphagia † 1	8/270 (2.96%)	13/267 (4.87%)
General disorders
Fatigue † 1	62/270 (22.96%)	57/267 (21.35%)
Asthenia † 1	46/270 (17.04%)	35/267 (13.11%)
Pyrexia † 1	30/270 (11.11%)	25/267 (9.36%)
Oedema peripheral † 1	12/270 (4.44%)	17/267 (6.37%)
Investigations
Weight decreased † 1	43/270 (15.93%)	31/267 (11.61%)
Metabolism and nutrition disorders
Decreased appetite † 1	197/270 (72.96%)	83/267 (31.09%)
Musculoskeletal and connective tissue disorders
Back pain † 1	8/270 (2.96%)	14/267 (5.24%)
Nervous system disorders
Neuropath peripheral † 1	51/270 (18.89%)	54/267 (20.22%)
Peripheral sensory neuropathy † 1	34/270 (12.59%)	29/267 (10.86%)
Dizziness † 1	14/270 (5.19%)	14/267 (5.24%)
Paraesthesia † 1	10/270 (3.70%)	13/267 (4.87%)
Headache † 1	6/270 (2.22%)	14/267 (5.24%)
Psychiatric disorders
Insomnia † 1	13/270 (4.81%)	11/267 (4.12%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	12/270 (4.44%)	18/267 (6.74%)
Dyspnoea † 1	13/270 (4.81%)	12/267 (4.49%)
Skin and subcutaneous tissue disorders
Palmer-plantar erythrodysaesthesia syndrom † 1	53/270 (19.63%)	34/267 (12.73%)
Rash † 1	57/270 (21.11%)	20/267 (7.49%)
Pruritus † 1	18/270 (6.67%)	5/267 (1.87%)
Skin hyperpigmentation † 1	14/270 (5.19%)	5/267 (1.87%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.

Results Point of Contact

• Name/Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chu MP, Hecht JR, Slamon D, Wainberg ZA, Bang YJ, Hoff PM, Sobrero A, Qin S, Afenjar K, Houe V, King K, Koski S, Mulder K, Hiller JP, Scarfe A, Spratlin J, Huang YJ, Khan-Wasti S, Chua N, Sawyer MB. Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer: Secondary Analysis of the TRIO-013/LOGiC Randomized Clinical Trial. JAMA Oncol. 2017 Jun 1;3(6):767-773. doi: 10.1001/jamaoncol.2016.3358. Erratum In: JAMA Oncol. 2017 Dec 1;3(12):1742.

Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, Jeziorski K, Shparyk Y, Hoff PM, Sobrero A, Salman P, Li J, Protsenko SA, Wainberg ZA, Buyse M, Afenjar K, Houe V, Garcia A, Kaneko T, Huang Y, Khan-Wasti S, Santillana S, Press MF, Slamon D. Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial. J Clin Oncol. 2016 Feb 10;34(5):443-51. doi: 10.1200/JCO.2015.62.6598. Epub 2015 Nov 30.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT00680901
• Other Study ID Numbers: EGF110656; 2007-005725-29 ( EudraCT Number ); CLAP016C2301 ( Other Identifier: Novartis )
• First Submitted: May 15, 2008
• First Posted: May 20, 2008
• Results First Submitted: May 16, 2013
• Results First Posted: October 29, 2013
• Last Update Posted: April 3, 2024