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

Study Overview

• Status: Active, not recruiting
• 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

Inclusion Criteria:

Signed informed consent; Histologically confirmed gastric, esophageal, or gastro-esophageal junction adenocarcinoma; disease that is locally advanced (unresectable), metastatic, or locally recurrent disease; Measurable or non-measurable, but radiologically evaluable disease, according to RECIST; ErbB2 (HER2)positive; Age =18 years; ECOG Performance status = 2; Adequate organ function, including adequate hematologic, renal and liver function; Cardiac ejection fraction within institutional range of normal as measured by echocardiogram; Able to swallow and retain oral medications, and/or receive enteral medications via gastrectomy feeding tube; Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study; Prior gastric surgery is permitted if > 3 weeks prior and recovered; Prior chemotherapy for non-gastric malignancy if > than 5 years; Prior neoadjuvant and/or adjuvant chemotherapy for early stage gastric cancer if > 6 months since completion; At least 4 weeks since prior radiotherapy; Prior biologic, hormonal, or immunologic cancer treatment if > 5 years since treatment.

Exclusion Criteria:

Pregnant or lactating females; Known history of active CNS disease; Uncontrolled ascites; Concurrent anti-cancer therapy; Gastric carcinoid, epidermoid, sarcomas, or squamous cell carcinoma; Prior palliative chemotherapy for the treatment of gastric cancer; Prior treatment with oxaliplatin < 12 months; Malabsorption syndrome or uncontrolled inflammatory gastrointestinal disease; Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; Pre-existing grade = 2 motor or sensory neuropathy; Uncontrolled infection; Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical condition that would interfere with the subject''s safety; Active hepatic or biliary disease; History of other malignancy except if disease-free for 5 years, a history of completely resected non-melanoma skin cancer, or a successfully treated in situ carcinoma; Unresolved or unstable serious toxicity from prior administration of another investigational drug and/or prior cancer treatment; Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent; Known history of DPD deficiency; Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib, capecitabine, fluorouracil, platins or their excipients; Use of any investigational drug within 30 days prior randomization; Use of concurrent prohibited medications that would interact with study medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• 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; Tyverb; 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	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.	From randomization until death due to any cause (average of 51 weeks)
Overall Survival in All Randomized Participants	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.	From randomization until death due to any cause (average of 51 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	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.	From randomization until the earliest date of disease progression or death due to any cause (average of 30 weeks)
Number of Participants With a Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR)	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).	From randomization until the date of the first documented response of CR or PR (average of 9 weeks)
Number of Participants With Clinical Benefit (CB)	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.	From randomization until disease progression (PD) or death due to any cause (average of 30 weeks)
Time to Response (TTR)	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.	From Baseline (Day 1) until the first documented evidence of confirmed CR or PR (average of 9 weeks)
Duration of Response (DOR)	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.	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)
Number of Participants With Any Non-serious Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) or Any Serious Adverse Event (SAE)	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.	From the first dose of study medication until 30 days after the last dose (average of 229 days)
Number of Participants With Adverse Events of the Indicated Severity, Per the National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE)	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.	From the first dose of study medication until 30 days after the last dose (average of 229 days)
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	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.	From Baseline (Day1) to Week 36
Mean Change in Scores on the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) From Baseline to Week 36	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.	From Baseline (Day1) to Week 36
Mean Change in Scores on the Questionnaire EuroQoL-5 Dimensions (EQ-5D) From Baseline to Week 36	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.	From Baseline (Day1) to Week 36
Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Clinical Chemistry Parameters	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]).	From Baseline (Day 1) until 28 days after the last dose (average of 239 days)
Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Hematology Parameters	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.	From Baseline (Day 1) until 28 days after the last dose (average of 239 days)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2008
• Primary Completion (Actual): September 24, 2012
• Study Completion (Estimated): August 22, 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): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: capecitabine; oxaliplatin; HER2; metastatic; lapatinib; ErbB2; unresectable; GE junction; TYVERB; TYKERB; CapeOx; gastric/esophageal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine 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