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

A Phase III Study for ErbB2 Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Junction Adenocarcinoma Treated With Capecitabine Plus Oxaliplatin With or Without Lapatinib

This was an international multi-center trial that enrolled patients with locally advanced, unresectable, or metastatic gastric, esophageal, or gastro-esophageal junction cancer whose tumors had amplification of the ErbB2 (HER2) gene. The trial investigated whether lapatinib, when added to the chemotherapy regimen, capecitabine plus oxaliplatin (CapeOx), extended the time to progression and overall survival. Tumor ErbB2 (HER2) status had to be known before trial entry. CapeOx was administered to all patients, and patients were randomly assigned to receive either lapatinib or placebo.

Study Overview

• Status: Completed
• Conditions: Neoplasms, Gastrointestinal Tract
• Intervention / Treatment: Drug: Lapatinib; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 545
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aires, Argentina, 1264
    • Novartis Investigative Site
  • La Rioja, Argentina, F5300COE
    • Novartis Investigative Site
  • Santa Fe, Argentina, 3000
    • Novartis Investigative Site
  • Tucuman, Argentina, 4000
    • Novartis Investigative Site
  • Buenos Aires
    • Ciudad Aut6noma de Buenos Aires, Buenos Aires, Argentina, C1050AAK
      • Novartis Investigative Site
    • Quilmes, Buenos Aires, Argentina, 1878
      • Novartis Investigative Site
  • Neuquén
    • Neuquen, Neuquén, Argentina, Q8300HDH
      • Novartis Investigative Site
  • Río Negro
    • Cipolletti, Río Negro, Argentina, R8324EMB
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000KZE
      • Novartis Investigative Site
• Brazil
  • Rio de Janeiro, Brazil, 20230-130
    • Novartis Investigative Site
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-281
      • Novartis Investigative Site
    • Belo Horizonte, Minas Gerais, Brazil, 30110-090
      • Novartis Investigative Site
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90050-170
      • Novartis Investigative Site
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-001
      • Novartis Investigative Site
  • Santa Catarina
    • Florianopolis, Santa Catarina, Brazil, 88034-000
      • Novartis Investigative Site
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Novartis Investigative Site
    • Jau, São Paulo, Brazil, 17210-120
      • Novartis Investigative Site
    • Santo Andre, São Paulo, Brazil, 09060-650
      • Novartis Investigative Site
    • Sao Paulo, São Paulo, Brazil, 01221-020
      • Novartis Investigative Site
    • Sao Paulo, São Paulo, Brazil, 01246-000
      • Novartis Investigative Site
    • Sao Paulo, São Paulo, Brazil, 01308-500
      • Novartis Investigative Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Novartis Investigative Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Novartis Investigative Site
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Novartis Investigative Site
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4C 3E7
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5B 1W8
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3G 1A4
      • Novartis Investigative Site
• Chile
  • Santiago, Chile, 7510032
    • Novartis Investigative Site
  • Región De La Araucania
    • Temuco, Región De La Araucania, Chile, 481-0469
      • Novartis Investigative Site
  • Región Metro De Santiago
    • Santiago, Región Metro De Santiago, Chile, 7500921
      • Novartis Investigative Site
  • Valparaíso
    • Vina del Mar, Valparaíso, Chile, 254-0364
      • Novartis Investigative Site
• China
  • Beijing, China, 100021
    • Novartis Investigative Site
  • Beijing, China, 100071
    • Novartis Investigative Site
  • Beijing, China, 100853
    • Novartis Investigative Site
  • Fuzhou, China, 350025
    • Novartis Investigative Site
  • Hangzhou, China, 310016
    • Novartis Investigative Site
  • Qingdao, China, 266061
    • Novartis Investigative Site
  • Shanghai, China, 200080
    • Novartis Investigative Site
  • Shanghai, China, 200032
    • Novartis Investigative Site
  • Tianjin, China, 300060
    • Novartis Investigative Site
  • Anhui
    • Hefei, Anhui, China, 230022
      • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Novartis Investigative Site
  • Heilongjiang
    • Ha Er Bin, Heilongjiang, China, 150040
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Novartis Investigative Site
  • Jilin
    • Changchun, Jilin, China, 130012
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
• Estonia
  • Tallinn, Estonia, 13419
    • Novartis Investigative Site
  • Tartu, Estonia, 51014
    • Novartis Investigative Site
• Hong Kong
  • Pokfulam, Hong Kong
    • Novartis Investigative Site
  • Tuen Mun, Hong Kong
    • Novartis Investigative Site
• Hungary
  • Gyor, Hungary, H-9024
    • Novartis Investigative Site
  • Kaposvar, Hungary, 7400
    • Novartis Investigative Site
  • Kecskemet, Hungary, 6000
    • Novartis Investigative Site
  • Miskolc, Hungary, 3526
    • Novartis Investigative Site
  • Pecs, Hungary, 7624
    • Novartis Investigative Site
  • Szeged, Hungary, 6720
    • Novartis Investigative Site
  • Szolnok, Hungary, 5004
    • Novartis Investigative Site
• India
  • Calcutta, India, 700026
    • Novartis Investigative Site
  • Coimbatore, India, 641037
    • Novartis Investigative Site
  • Kochi, India, 682041
    • Novartis Investigative Site
  • Kochi, India
    • Novartis Investigative Site
  • Kolkata, India, 700 053
    • Novartis Investigative Site
  • Nagpur, India, 440010
    • Novartis Investigative Site
  • New Delhi, India
    • Novartis Investigative Site
  • Parel, India, 400012
    • Novartis Investigative Site
  • Pune, India, 411001
    • Novartis Investigative Site
  • Trivandrum, India, 695011
    • Novartis Investigative Site
• Israel
  • Beer-Sheva, Israel, 84101
    • Novartis Investigative Site
  • Haifa, Israel, 31096
    • Novartis Investigative Site
  • Jerusalem, Israel, 91031
    • Novartis Investigative Site
  • Petah-Tikva, Israel, 49100
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Rehovot, Israel, 76100
    • Novartis Investigative Site
  • Tel Aviv, Israel, 64239
    • Novartis Investigative Site
  • Zrifin, Israel, 70300
    • Novartis Investigative Site
• Italy
  • Macerata, Italy
    • Novartis Investigative Site
  • Abruzzo
    • L'Aquila, Abruzzo, Italy, 67100
      • Novartis Investigative Site
  • Basilicata
    • Rionero In Vulture (PZ), Basilicata, Italy, 85028
      • Novartis Investigative Site
  • Emilia-Romagna
    • Cesena, Emilia-Romagna, Italy, 47023
      • Novartis Investigative Site
    • Meldola (FC), Emilia-Romagna, Italy, 47014
      • Novartis Investigative Site
    • Modena, Emilia-Romagna, Italy, 41100
      • Novartis Investigative Site
    • Parma, Emilia-Romagna, Italy, 43100
      • Novartis Investigative Site
    • Piacenza, Emilia-Romagna, Italy, 29100
      • Novartis Investigative Site
    • Rimini, Emilia-Romagna, Italy, 47900
      • Novartis Investigative Site
  • Friuli-Venezia-Giulia
    • Udine, Friuli-Venezia-Giulia, Italy, 33100
      • Novartis Investigative Site
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Novartis Investigative Site
    • Roma, Lazio, Italy, 00161
      • Novartis Investigative Site
    • Roma, Lazio, Italy, 00152
      • Novartis Investigative Site
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Novartis Investigative Site
  • Lombardia
    • Bergamo, Lombardia, Italy, 24128
      • Novartis Investigative Site
    • Treviglio (BG), Lombardia, Italy, 24047
      • Novartis Investigative Site
  • Marche
    • Pesasro, Marche, Italy, 61122
      • Novartis Investigative Site
  • Puglia
    • Bari, Puglia, Italy, 70124
      • Novartis Investigative Site
  • Toscana
    • Firenze, Toscana, Italy, 50139
      • Novartis Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 602-030
    • Novartis Investigative Site
  • Daegu, Korea, Republic of, 700-712
    • Novartis Investigative Site
  • Hwasun, Korea, Republic of, 519-809
    • Novartis Investigative Site
  • Seodaemun-gu, Seoul, Korea, Republic of, 120-752
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 135-710
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 136-705
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 110-744
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 135-720
    • Novartis Investigative Site
  • Suwon, Korea, Republic of, 442-723
    • Novartis Investigative Site
  • Suwon, Kyonggi-do, Korea, Republic of, 443-721
    • Novartis Investigative Site
• Mexico
  • Mexico City, Mexico, CP 14080
    • Novartis Investigative Site
  • Oaxaca, Mexico, 68000
    • Novartis Investigative Site
  • Guerrero
    • Acapulco, Guerrero, Mexico, 39670
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Novartis Investigative Site
  • Leeuwarden, Netherlands, 8934 AD
    • Novartis Investigative Site
  • Nijmegen, Netherlands, 6525 GA
    • Novartis Investigative Site
• Peru
  • Callao, Peru, Callao 2
    • Novartis Investigative Site
  • Lima, Peru, Lima 11
    • Novartis Investigative Site
  • Lima, Peru, Lima 34
    • Novartis Investigative Site
• Poland
  • Gdansk, Poland, 80-219
    • Novartis Investigative Site
  • Krakow, Poland, 31-501
    • Novartis Investigative Site
  • Olsztyn, Poland, 10-226
    • Novartis Investigative Site
  • Olsztyn, Poland, 10-513
    • Novartis Investigative Site
  • Plock, Poland, 09-400
    • Novartis Investigative Site
  • Poznan, Poland, 61-866
    • Novartis Investigative Site
  • Rybnik, Poland, 44-200
    • Novartis Investigative Site
  • Slupsk, Poland, 76-200
    • Novartis Investigative Site
  • Szczecin, Poland, 70-111
    • Novartis Investigative Site
  • Torun, Poland, 87-100
    • Novartis Investigative Site
  • Warszawa, Poland, 02-781
    • Novartis Investigative Site
  • Warszawa, Poland, 02-507
    • Novartis Investigative Site
• Puerto Rico
  • San Juan, Puerto Rico, 00910
    • Novartis Investigative Site
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Novartis Investigative Site
  • Kirov, Russian Federation, 610021
    • Novartis Investigative Site
  • Kursk, Russian Federation, 305035
    • Novartis Investigative Site
  • Moscow, Russian Federation, 115478
    • Novartis Investigative Site
  • Omsk, Russian Federation, 644013
    • Novartis Investigative Site
  • Ryazan, Russian Federation, 390011
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410004
    • Novartis Investigative Site
  • Sochi, Russian Federation, 354057
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 197758
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 198255
    • Novartis Investigative Site
  • Stavropol, Russian Federation, 355047
    • Novartis Investigative Site
  • Ufa,, Russian Federation, 450054
    • Novartis Investigative Site
• Taiwan
  • Tainan, Taiwan, 704
    • Novartis Investigative Site
  • Taipei, Taiwan, 104
    • Novartis Investigative Site
  • Taipei, Taiwan, 112
    • Novartis Investigative Site
  • Taoyuan County, Taiwan, 333
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Hatyai, Songkhla, Thailand, 90110
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06500
    • Novartis Investigative Site
  • Gaziantep, Turkey, 27310
    • Novartis Investigative Site
  • Trabzon, Turkey, 61187
    • Novartis Investigative Site
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Novartis Investigative Site
  • Chernivtsi, Ukraine, 58013
    • Novartis Investigative Site
  • Dnepropetrovsk, Ukraine, 49102
    • Novartis Investigative Site
  • Dnipropetrovsk, Ukraine, 49100
    • Novartis Investigative Site
  • Donetsk, Ukraine, 83092
    • Novartis Investigative Site
  • Ivano-Frankivsk, Ukraine, 76018
    • Novartis Investigative Site
  • Kharkiv, Ukraine, 61070
    • Novartis Investigative Site
  • Kryvyi Rih, Ukraine, 50048
    • Novartis Investigative Site
  • Kyiv, Ukraine, 03115
    • Novartis Investigative Site
  • Kyiv, Ukraine, 03022
    • Novartis Investigative Site
  • Kyiv, Ukraine, 04107
    • Novartis Investigative Site
  • Lutsk,, Ukraine, 43018
    • Novartis Investigative Site
  • Lviv, Ukraine, 79031
    • Novartis Investigative Site
  • Odessa, Ukraine, 65055
    • Novartis Investigative Site
  • Plyuty, Ukraine, 08720
    • Novartis Investigative Site
  • Simferopil, Ukraine, 95023
    • Novartis Investigative Site
  • Simferopol, Ukraine, 95023
    • Novartis Investigative Site
  • Sumy, Ukraine, 40005
    • Novartis Investigative Site
  • Ternopil, Ukraine, 46023
    • Novartis Investigative Site
  • Uzhgorod, Ukraine, 88000
    • Novartis Investigative Site
  • Vinnitsia, Ukraine, 21029
    • Novartis Investigative Site
  • Zaporizhzhia, Ukraine, 69040
    • Novartis Investigative Site
• United States
  • California
    • Alhambra, California, United States, 91801
      • Novartis Investigative Site
    • Fullerton, California, United States, 92835
      • Novartis Investigative Site
    • La Verne, California, United States, 91750
      • Novartis Investigative Site
    • Northridge, California, United States, 91328
      • Novartis Investigative Site
    • Oxnard, California, United States, 93030
      • Novartis Investigative Site
    • Redondo Beach, California, United States, 90277
      • Novartis Investigative Site
    • Santa Maria, California, United States, 93454
      • Novartis Investigative Site
    • Santa Monica, California, United States, 90404
      • Novartis Investigative Site
  • Indiana
    • Terre Haute, Indiana, United States, 47802
      • Novartis Investigative Site
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key inclusion criteria:

• Histologically confirmed gastric adenocarcinoma or adenocarcinoma of the esophagus or gastro-esophageal junction.
• Gastric cancer that is unresectable due to locally advanced (defined as stage IV: T4N1-3 or TanyN3), metastatic, or locally recurrent disease; Esophageal cancer that is unresectable due to locally advanced (T3N1 or T4Nany), metastatic or locally recurrent disease.
• Measurable or non-measurable, but radiologically evaluable disease, according to RECIST.
• HER2 amplification by FISH assessed by the local or designated central laboratory; Subjects with unknown HER2 status were not eligible.
• Adequate organ function, as defined in the study protocol, assessed within 14 days prior randomization.
• Cardiac ejection fraction within institutional range of normal as measured by echocardiogram (ECHO).

• Prior/Concurrent Therapy:

  • At least 3 weeks following major surgery, such as gastrectomy, and were recovered from any related toxicity More than 5 years since prior chemotherapy for malignancy other than GC. At least 4 weeks since prior radiotherapy
  • More than 5 years since prior biologic or hormonal therapy or immunotherapy for malignancy other than gastric carcinoma.

Key exclusion criteria:

• Pregnant or lactating females at any time during the study.
• Known history of active CNS disease.
• Uncontrolled ascites.
• Concurrent anti-cancer therapy (chemotherapy, radiation therapy other than for pain relief, immunotherapy, biologic therapy, hormonal therapy or surgery) while taking investigational treatment.
• Gastric carcinoid, epidermoid, sarcomas, or squamous cell carcinoma.
• Prior palliative chemotherapy for the treatment of gastric cancer.
• Prior treatment with oxaliplatin-based neoadjuvant or adjuvant chemotherapy completed <12 months.
• Malabsorption syndrome or uncontrolled inflammatory gastrointestinal disease (such as Crohn's disease or ulcerative colitis).
• Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure.
• Uncontrolled infection.
• History of other malignancy. However, subjects who were disease-free for 5 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, were eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CapeOx plus Lapatinib	Drug: Lapatinib; 5 pills at 250mg each once daily; Other Names: Tykerb; Drug: Capecitabine; 1700mg/m2/day in two daily doses; Drug: Oxaliplatin; 130mg/m2 on day 1
Placebo Comparator: CapeOx plus Placebo	Drug: Capecitabine; 1700mg/m2/day in two daily doses; Drug: Oxaliplatin; 130mg/m2 on day 1; Drug: Placebo; 5 pills once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival at the Time of Primary Analysis	Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.	From date of randomization till death due to any cause, assessed up the cut-off date for Primary Analysis (24-Sep-2012) (average of 4 years)
Overall Survival in All Randomized Participants at the Time of Primary Analysis	Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.	From date of randomization till death due to any cause, assessed up the cut-off date for Primary Analysis (24-Sep-2012) (average of 4 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival at the Time of Final Analysis	Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.	From date of randomization till death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Progression Free Survival (PFS)	Progression-Free Survival (PFS) was defined as the time from randomization to the earliest occurrence of disease progression or death from any cause. Per RECIST v1.0, progression was defined as at least a 20% increase in the sum of diameters of target lesions from the smallest recorded sum or the appearance of one or more new lesions. Participants with symptomatic progression, even without radiological confirmation, were also counted. Those who had neither progressed nor died were censored at their follow-up visit, either because follow-up had ended or was ongoing. Participants who received non-study anti-cancer therapies before progression were also censored.	From date of randomization till the earliest date of disease progression or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Percentage of Participants With a Confirmed Complete Response (CR) or a Partial Response (PR)	A participant was considered a responder if they had achieved either a complete response (CR), defined as the disappearance of all target and non-target lesions, or a partial response (PR), defined as at least a 30% reduction in the sum of the longest diameters of target lesions from baseline, as assessed by the investigator and confirmed by radiographic imaging within four weeks of the initial observation.	From date of randomization till the date of the first documented response of CR or PR, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Percentage of Participants With Clinical Benefit (CB)	Clinical Benefit (CB) was defined as evidence of a complete response (CR), partial response (PR), or stable disease (SD). CR referred to the disappearance of all target and non-target lesions, PR to at least a 30% reduction in the sum of the longest diameters of target lesions from baseline, and SD to neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression, based on the smallest sum of diameters recorded since treatment initiation. All assessments were made by the investigator.	From date of randomization till date of disease progression (PD) or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Time to Response (TTR)	Time to Response (TTR) was defined as the duration from randomization to the first documented evidence of either a complete response (CR) (the disappearance of all target and non-target lesions) or a partial response (PR) (at least a 30% reduction in the sum of the longest diameters of target lesions from baseline) as assessed by the investigator.	From date of randomization till the first documented evidence of confirmed CR or PR, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Duration of Response (DOR)	Duration of Response (DOR) was defined as the time from the first documented evidence of a complete response (CR) or partial response (PR) until the first recorded sign of disease progression or death from any cause. According to RECIST, progression was defined as at least a 20% increase in the sum of diameters of target lesions from the smallest recorded sum or the appearance of one or more new lesions. Participants who had neither progressed nor died were censored at their follow-up visit, either because follow-up had ended or was ongoing. Those who received non-study anti-cancer therapies before progression were also censored.	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, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Percentage of Participants With Any On-therapy Adverse Event (AE) and Serious Adverse Event (SAE)	An Adverse Event (AE) was defined as any untoward medical occurrence in a participant that was temporally associated with the use of a medicinal product, regardless of its causal relationship. This included any unfavorable or unintended sign (such as abnormal lab findings), symptom, or disease, whether new or worsened. A Serious Adverse Event (SAE) was defined as any such occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or its prolongation, caused disability or incapacity, led to a congenital anomaly or birth defect, or was a potential case of drug-induced liver injury.	From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade	An Adverse Event (AE) was defined as any untoward medical occurrence in a participant that was temporally associated with the use of a medicinal product, regardless of its relationship to the product. This included any unfavorable or unintended sign (such as abnormal lab results), symptom, or disease, whether new or worsened. The severity of AEs was graded according to NCI CTCAE version 3.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death related to toxicity).	From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade	A Serious Adverse Event (SAE) was defined as any such occurrence that resulted in death, was life-threatening, required hospitalization or its prolongation, caused disability or incapacity, led to a congenital anomaly or birth defect, or was a potential case of drug-induced liver injury. The severity of SAEs was graded according to NCI CTCAE version 3.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death related to toxicity).	From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores	The EORTC QLQ-C30 is a comprehensive questionnaire developed for assessing the quality of life of cancer patients across different aspects including function scales namely physical, role, cognitive, emotional and social; symptom scales such as fatigue, pain, nausea and vomiting; and a global scale pronouncing overall health status. Its scoring method involves a 4-point Likert scale (ranging from 1 'Not at all' to 4 'Very Much'). Domain scores are calculated by averaging the items within the respective domain and then linearly transforming the score to fit within a 0-100 scale to finalize the scores. In terms of interpretation, a high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.	From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale	The QLQ-STO22 consists of 22 items divided into five subscales: dysphagia, pain, reflux, eating restrictions and anxiety, as well as single items addressing dry mouth, body image, taste, and hair loss. Each item is answered on a 4-point scale, ranging from 1 (not at all) to 4 (very much). Raw scores for each subscale or single item are calculated by averaging the scores of the individual items that make up the scale. These scores are then linearly transformed to range from 0 to 100. In terms of interpretation, a higher score indicates a worse quality of life concerning the specific symptoms assessed.	From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Mean Change From Baseline in Utility Score (Health Utility Index) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire	The EQ-5D is a standardized instrument developed by the EuroQoL Group to measure health-related quality of life. It includes a descriptive system covering five dimensions and a Visual Analogue Scale (VAS), often referred to as the Thermometer Score. The Utility Score (Health Utility Index) is derived from the five dimensions of the EQ-5D descriptive system (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has levels indicating severity (e.g., 1 = no problems, 2 = some problems, 3 = extreme problems). These combinations form a health state, which is then converted into a single index value using a country-specific value set. In the UK-based value set, the possible EQ-5D index utility values range from -0.594 to 1.0, where: 1.0 = perfect health, 0 = death and < 0 = health states considered worse than death.	From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Mean Change From Baseline in Thermometer Score (EQ VAS) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire	The EQ-5D is a standardized instrument developed by the EuroQol Group to measure health-related quality of life. It includes a descriptive system covering five dimensions and a Visual Analogue Scale (VAS), often referred to as the Thermometer Score. The Thermometer Score is a self-rated health score using a vertical visual analogue scale , where respondents rate their overall health on a scale from 0 (worst imaginable health) to 100 (best imaginable health).	From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Percentage of Participants With Worst-case On-therapy Chemistry Toxicities	The severity of chemistry parameters was graded according to NCI CTCAE version 3.0: Grade 0 (No adverse event or within normal limits), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life-threatening). Chemistry data included: Alanine aminotransferase (ALT), Albumin, Alkaline phosphatases (ALP), Aspartate aminotransferase (AST), Calcium (hypercalcemia), Calcium (hypocalcemia), Creatine Kinase (CK), Creatine, Glucose (hyperglycemia), Glucose (hypoglycemia), Magnesium (hypermagnesemia), Magnesium (hypomagnesemia), Potassium (hyperkalemia), Potassium (hypokalemia), Sodium (hypernatremia), Sodium (hyponatremia) and Total Bilirubin.	From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Percentage of Participants With Worst-case On-therapy Hematologic Toxicities	The severity of hematologic parameters was graded according to NCI CTCAE version 3.0: Grade 0 (No adverse event or within normal limits), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life-threatening). Hematology data included: Hemoglobin, Platelet count, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) and White Blood Cell count.	From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2008
• Primary Completion (Actual): September 24, 2012
• Study Completion (Actual): October 3, 2024

Study Registration Dates

• First Submitted: May 15, 2008
• First Submitted That Met QC Criteria: May 15, 2008
• First Posted (Estimated): May 20, 2008

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: July 17, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: capecitabine; oxaliplatin; HER2; metastatic; lapatinib; ErbB2; unresectable; GE junction; TYKERB; CapeOx; gastric/esophageal cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Protein Kinase Inhibitors; Capecitabine; Oxaliplatin; Lapatinib
• Other Study ID Numbers: EGF110656; 2007-005725-29 (EudraCT Number); CLAP016C2301 (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No