A Study of Trastuzumab Emtansine Versus Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer

Gastric Cancer Clinical Trial

Official title:

A Randomized, Multicenter, Adaptive Phase II/III Study To Evaluate The Efficacy And Safety Of Trastuzumab Emtansine (T-DM1) Versus Taxane (Docetaxel Or Paclitaxel) In Patients With Previously Treated Locally Advanced Or Metastatic HER2-Positive Gastric Cancer, Including Adenocarcinoma Of The Gastroesophageal Junction

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01641939
• Other study ID #: BO27952
• Secondary ID: 2012-000660-22
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: July 13, 2012
• Last updated: May 5, 2017
• Start date: September 3, 2012
• Est. completion date: April 30, 2016

Study information

• Verified date: May 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multicenter, randomized, adaptive Phase II/III study will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) compared to standard taxane (docetaxel or paclitaxel) treatment in participants with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. At the start of the trial (stage 1), participants will be randomized with a ratio 2:2:1 to one of three treatment arms: Arm A: trastuzumab emtansine 3.6 milligram per kilogram (mg/kg) per intravenous injection (IV) every 3 weeks; Arm B: trastuzumab emtansine 2.4 mg/kg IV every week; Arm C: standard taxane therapy (docetaxel 75 milligram per meter square [mg/m^2] IV every 3 weeks or paclitaxel 80 mg/m^2 kg IV every week per investigator choice). At the end of the first stage of the study, the dose and schedule of trastuzumab emtansine that will be used in the second stage of the study will be selected by an Independent Data Monitoring Committee (IDMC). The regimen selection analysis will be made after approximately 100 participants across all three study arms have been treated for at least 12 weeks.

Once a trastuzumab emtansine regimen has been selected, Stage I participants who were assigned to the treatment arm which was selected for Stage II of the study and participants who were in the standard taxane group will continue to receive their assigned treatment regimen. Stage I participants who were assigned to the regimen that was not selected for further evaluation will continue to receive their assigned regimen and will continue to be followed for efficacy and safety. In Stage II of the study, additional participants will be recruited and randomized with a ratio 2:1 to either the selected regimen of trastuzumab emtansine or to the standard taxane therapy. Participants will receive study treatment until disease progression, unacceptable toxicity, initiation of another cancer therapy or withdrawal.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 415
• Est. completion date: April 30, 2016
• Est. primary completion date: June 30, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Life expectancy of at least 12 weeks from the first dose of study treatment

• Measurable and/or evaluable disease based on Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)

• Adequate organ function as determined by the following laboratory results, within 28 days prior to randomization

• Participants must have a history of advanced gastric cancer (AGC), defined as unresectable and locally advanced or metastatic gastric cancer, including adenocarcinoma of the gastroesophageal junction (GEJ), and must have experienced disease progression during or after first-line therapy for their disease

• HER2-positive tumor (primary tumor or metastatic lesion) as confirmed by central laboratory HER2 testing (immunohistochemistry and/or in-situ hybridization)

• Participants must have received at least one prior chemotherapy regimen for AGC; prior therapy does not need to have included HER2-directed therapy.

• First-line therapy for AGC, including adenocarcinoma of the GEJ, must have included a combination of at least a platinum- and a fluoropyrimidine-based treatment given concurrently; prior therapy does not need to have included a HER2-directed therapy.

• Adjuvant or neoadjuvant therapy for AGC is allowed.

Exclusion Criteria:

• An interval shorter than 21 days from the last dose of chemotherapy or HER2-directed therapy until the time of randomization

• Prior treatment with trastuzumab emtansine, docetaxel, or paclitaxel either as single agents or as part of a treatment regimen.

• Treatment with any investigational anticancer drug within 21 days of the first study treatment administration

• More than one prior line of therapy for advanced gastric cancer

• History of other malignancy within the previous 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome

• Brain metastases that are untreated or symptomatic or require any radiation, surgery, or steroid therapy to control symptoms from brain metastases within 1 month of randomization

• Peripheral neuropathy Grade >/=2

• Uncontrolled cardiopulmonary dysfunction (e.g., high blood pressure, serious cardiac arrhythmia)

• Other current, severe, uncontrolled systemic disease (e.g., clinically significant metabolic disease, wound healing disorders, ulcers)

• Clinically significant bleeding within 30 days before enrollment

• For female participants, current pregnancy or lactation

• Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment

• Infection with Human immunodeficiency virus (HIV) or hepatitis B virus, hepatitis C virus

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Taxane
Standard taxane (docetaxel 75 mg/m^2 IV every 3 weeks or paclitaxel 80 mg/m^2) IV once a week according to investigator choice.
• trastuzumab emtansine
trastuzumab emtansine 3.6 mg/kg IV every 3 weeks
• trastuzumab emtansine
trastuzumab emtansine 2.4 mg/kg IV once a week

Locations

Country	Name	City	State
Argentina	Fundación Investigar	Buenos Aires
Argentina	Hospital de Gastroenterologia Dr. Bonorino Udaondo ; Servicio de Oncología	Buenos Aires
Argentina	Instituto de Oncología de Rosario	Rosario
Belgium	UZ Leuven Gasthuisberg	Leuven
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Hospital Amaral Carvalho	Jau	SP
Brazil	Clinica de Oncologia de Porto Alegre - CliniOnco	Porto Alegre	RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Instituto Nacional de Cancer - INCa; Oncologia	Rio de Janeiro	RJ
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Brazil	Instituto de Oncologia de Sorocaba - CEPOS	Sorocaba	SP
Canada	Brampton Memorial Hospital, William Osler Health Center	Brampton	Ontario
Canada	St. Michael'S Hospital	Toronto	Ontario
Canada	Toronto East General Hospital; Haematology/Oncology	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
China	Beijing Cancer Hospital	Beijing
China	The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)	Beijing
China	Jilin Cancer Hospital	Changchun
China	the First Hospital of Jilin University	Changchun
China	Changzhou First People's Hospital	Changzhou
China	Third Affiliated Hospital of Third Military Medical University	ChongQing
China	Fujian Cancer Hospital	Fuzhou
China	Sun Yet-sen University Cancer Center	Guangzhou
China	Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Jiangsu Cancer Hospital	Nanjing
China	The 81st Hospital of P.L.A.	Nanjing
China	Affiliated Hospital of Nantong University	Nantong
China	Fudan University Shanghai Cancer Center	Shanghai
China	Shanghai First People's Hospital	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
China	General Hospital of Shenyang Military Command of PLA	Shenyang
China	Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center	Wuhan
China	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou
Czechia	Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology	Hradec Kralove
Czechia	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc
Czechia	Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika	Praha 2
Czechia	Fakultní Nemocnice V Motole; Radioterapeuticko-Onkologicke Oddeleni	Praha 5
Finland	Tampere University Hospital; Dept of Oncology	Tampere
France	Hopital Augustin Morvan; Federation De Cancerologie	Brest
France	Hopital Beaujon; Gastro Enterologie 1	Clichy
France	Centre Val Aurelle Paul Lamarque; Medecine A1 A2	Montpellier
France	Hop Europeen Georges Pompidou; Gastro Enterologie	Paris
France	Hopital Saint Antoine; Hepatologie-Gastr-Enterologie	Paris
France	Hopital Robert Debre; Gastro Enterologie	Reims
France	Hopital Purpan; Unite Onco Digestive	Toulouse
Germany	Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.	Berlin
Germany	Universitätsklinikum "Carl Gustav Carus"; Med. Klinik & Poliklinik I, Arbeitsgr. intern. Onkologie	Dresden
Germany	Facharztzentrum Eppendorf, Studien GbR	Hamburg
Germany	Universitätsklinikum Köln	Köln
Germany	Tagesklinik Landshut; Hämatologie/Onkologie	Landshut
Germany	Onkologische Gemeinschaftspraxis	Magdeburg
Guatemala	Centro Oncológico Sixtino / Centro Oncológico SA	Guatemala
Guatemala	Grupo Angeles	Guatemala City
Hungary	Fovarosi Szent Laszlo Korhaz-Rendelointezet; Onkologiai Osztaly X	Budapest
Hungary	Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika	Szeged
Hungary	Hetenyi Geza County Hospital; Onkologiai Kozpont	Szolnok
Hungary	Zala Megyei Kórház, Külsö Kórház, Pózva; Onkológiai Osztály	Zalaegerszeg
Italy	AZ.Osp S. Orsola - Malpighi-Reparto di Oncologia Medica	Bologna	Emilia-Romagna
Italy	Campus Universitario S.Venuta; Centro Oncologico T.Campanella	Catanzaro	Calabria
Italy	Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1	Firenze	Toscana
Italy	A.O. Universitaria Pisana; Oncologia	Pisa	Toscana
Italy	A.O. Città della Salute e della Scienza - Presidio Molinette; divisione oncologia medica	Torino	Piemonte
Japan	Aichi Cancer Center Hospital; Clinical Oncology	Aichi
Japan	Chiba Cancer Center; Gastroenterology	Chiba
Japan	National Cancer Center Hospital East; Gastroenterology	Chiba
Japan	National Hospital Organization Shikoku Cancer Center; Gastroenterology	Ehime
Japan	Hokkaido University Hospital:Gastroenterology	Hokkaido
Japan	Hyogo Cancer Center; Gastroenterology	Hyogo
Japan	Hyogo College Of Medicine; Upper Gastroenterology	Hyogo
Japan	Ibaraki Prefectural Central Hospital; Gastroenterology	Ibaraki
Japan	Tohoku Uni Hospital; Clinical Oncology	Miyagi
Japan	Kindai University Hospital; Medical Oncology	Osaka
Japan	Osaka University Hospital; Surgery	Osaka
Japan	Saitama Cancer Center; Gastroenterology	Saitama
Japan	Shizuoka Cancer Center; Gastroenterology	Shizuoka
Japan	Shizuoka General Hospital; Clinical Oncology	Shizuoka
Japan	Tochigi Cancer Center; Medical Oncology	Tochigi
Japan	National Cancer Center Hospital; Gastrointestinal Oncology	Tokyo
Japan	The Cancer Institute Hospital, JFCR; Gastroenterology	Tokyo
Japan	Tokyo Metropolitan Komagome Hospital; Chemotherapy	Tokyo
Japan	Toranomon Hospital; Medical Oncology	Tokyo
Korea, Republic of	Asan Medical Center; Medical Oncology	Seoul
Korea, Republic of	Korea University Anam Hospital; Oncology Haemotology	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St.Mary's Hospital; Medical Oncology	Seoul
Korea, Republic of	Yonsei University Severance Hospital; Medical Oncology	Seoul
Malaysia	University Malaya Medical Centre; Clinical Oncology Unit,	Kuala Lumpur
Malaysia	Hospital Wanita dan Kanak-Kanak Sabah	Sabah
Mexico	Centenario Hospital Miguel Hidalgo	Aguascalientes
Mexico	Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre	Chihuahua
Mexico	Hospital General de México; Unidad de Oncologia	Mexico DF
Panama	Centro Hemato Oncologico Paitilla	Panama City
Peru	Hospital Nacional Almanzor Aguinaga Asenjo; Unidad De Investigacion Del Servicio De Oncologia Medica	Chiclayo
Peru	Hospital Nacional Adolfo Guevara Velasco	Cusco
Peru	Hospital Nacional Edgardo Rebagliati Martins	Jesus Maria
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Philippines	Perpetual Succour Hospital	Cebu
Philippines	Veterans Memorial Medical Ctr; Cancer Research Centre	Quezon City, Luzon
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii	Gdansk
Poland	Szpital Uniwersytecki w Krakowie	Krakow
Poland	Wielkopolskie Centrum Onkologii; im. Marii Sklodowskiej-Curie	Poznan
Poland	Wojewódzki Szpital Specjalistyczny Nr 3	Rybnik
Poland	Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie; Klinika Gastroenterologii Onkologicznej	Warszawa
Romania	Institutul Clinic Fundeni Bucuresti	Bucharest
Romania	Medisprof SRL	Cluj-Napoca
Romania	Spitalul Universitar CF Cluj-Napoca; Sectia Oncologie	Cluj-Napoca
Romania	Spitalul Clinic Judetean Mures; Oncologie Medicala	Targu Mures
Russian Federation	Arkhangelsk Regional Clinical Oncology Dispensary	Arkhangelsk
Russian Federation	Ivanovo Regional Oncology Dispensary	Ivanovo
Russian Federation	Omsk Region Clinical Oncology Dispensary; 1St Sergical Department	Omsk
Russian Federation	State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary	Pyatigorsk
Russian Federation	Tula Regional Oncology Dispensary	Tula
Singapore	National Cancer Centre	Singapore
Spain	Hospital Clinic i Provincial; Servicio de Farmacia	Barcelona
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Univ. Central de Asturias; Servicio de Oncologia	Oviedo	Asturias
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	La Coruña
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza
Taiwan	Kaohsiung Chang Gung Memorial Hospital; Dept of Hem and Onc	Kaohsung
Taiwan	National Taiwan Uni Hospital; Dept of Oncology	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology	Taoyuan
Turkey	Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department	Erzurum
Turkey	Istanbul Bilim University School Of Medicine; Department Of Medical Oncology	Istanbul
Turkey	Marmara Uni Faculty of Medicine; Medical Oncology	Istanbul
Turkey	Ege Uni Medical Faculty; Oncology Dept	Izmir
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye, ANKARA
United Kingdom	Velindre Cancer Centre; Oncology Dept	Cardiff
United Kingdom	The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit	Glasgow
United Kingdom	Royal Marsden Hospital; Dept of Med-Onc	London
United Kingdom	Christie Hospital Nhs Trust; Medical Oncology	Manchester
United Kingdom	Royal Marsden Hospital; Dept of Medical Oncology	Sutton
United Kingdom	BRISTOL ONCOLOGY CENTRE; CLINICAL TRIALS UNIT; R & D department	Weston Super Mare
United States	Comprehensive Blood/Cancer Ctr	Bakersfield	California
United States	Dana Farber Can Ins	Boston	Massachusetts
United States	Massachusetts General Hospital.	Boston	Massachusetts
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Norton Healthcare Inc.	Louisville	Kentucky
United States	Vanderbilt	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Weill Cornell Medical College	New York	New York
United States	Stanford University School of Medicine	Stanford	California
United States	University of Kansas; Medical Center & Medical pavilion	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  China,  Czechia,  Finland,  France,  Germany,  Guatemala,  Hungary,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Panama,  Peru,  Philippines,  Poland,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)- Phase 3	Overall survival was defined as the time between the date of randomization and date of death due to any cause. Kaplan-Meier estimates were used for analysis. Participants for whom no death was reported prior to an analysis cutoff (30 June 2015) was censored at the latest date before the cutoff in which they were known to be alive. All data from the standard taxane therapy and trastuzumab emtansine 2.4 mg (selected treatment arm) from phase 2 and phase 3 (Stage 2) are combined into phase 3 data, and thus cumulative data are provided within the results presented for phase 3. The confirmatory analyses are restricted to comparisons between the taxane arm and the selected trastuzumab emtansine arm (2.4 mg).	Date of randomization until death (up to 2 years 3 months)
Primary	Overall Survival (OS) - Phase 2 (Dose Selection Portion of the Study)	Overall survival was defined as the time between the date of randomization and date of death due to any cause. Kaplan-Meier estimates were used for analysis. Participants for whom no death was reported prior to an analysis cutoff (10 August 2013) was censored at the latest date before the cutoff in which they were known to be alive.	Date of randomization until death (up to 1 year)
Secondary	Percentage of Participants With Disease Progression or Death According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1) - Phase 3	Progressive disease could base on symptom deterioration or was defined as at least a 20 percent (%) increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Tumor assessment was performed using modified RECIST v1.1. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.	Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months)
Secondary	Progression Free Survival (PFS) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1) - Phase 3	Progression-free survival was defined as the time between the date of randomization and the first date of documented progression or date of death due to any cause, whichever occurred first. Tumor assessment was performed using modified RECIST v1.1. Progressive disease could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Kaplan-Meier estimates were used for analysis. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure. The confirmatory analyses are restricted to comparisons between the taxane arm and the selected trastuzumab emtansine arm (2.4 mg).	Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months)
Secondary	Percentage of Participants With Objective Response According to mRECIST v1.1 - Phase 3	Objective response referred to participants with complete response (CR) or partial response (PR). CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: greater than or equal to (>=) 30% decrease in sum of the longest diameter (LD) of all target lesions taking as reference the screening sum LD. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed no less than 4 weeks after the criteria for response were first met. Longer intervals as determined by the study protocol were also appropriate. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.	Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months)
Secondary	Duration of Objective Response (DOR) - Phase 3	DOR: time from the date when a clinical response [CR or PR] was first documented to the date of first documented progressive disease (PD) or death. CR:disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: >= 30% decrease in sum of the LD of all target lesions taking as reference the screening sum LD. PD: could base on symptom deterioration or at least a 20% increase in the sum of diameters of target or non-target lesions and new lesions, taking as reference the smallest sum on study (nadir), including baseline. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed no less than 4 weeks after the criteria for response were first met. Longer intervals as determined by the study protocol were also appropriate. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.	Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months)
Secondary	Percentage of Participants With Clinically Significant Improvement in European Organisation for Research and Treatment of Cancer Quality of Life Core Module 30 (EORTC QLQ-C30) Score - Phase 3	The EORTC QLQ-C30 is a validated, cancer-specific 30-item patient-reported measure, and contains 14 domains to assess the impact of cancer treatment on 5 aspects of participants functioning (physical, role, cognitive, emotional, and social), 9 aspects of disease/treatment-related symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, diarrhea) and a global QoL/overall health status scale. Questions used 4 point scale (1 'Not at all' to 4 'Very much'; with the exception of the QoL/health status scale which uses a 7-point scale (1 'very poor' to 7 'Excellent'). Each scale is transformed on a scale of 0-100; a higher score equals (=) a better level of functioning or greater degree of symptoms. Change of greater than or equal to (>=) 10-points has been found to be clinically significant. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.	Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at follow-up (up to 2 years 3 months)
Secondary	Percentage of Participants With Clinically Significant Improvement in Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22) Score - Phase 3	The Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22) supplements the EORTC QLQ-C30 to assess symptoms and treatment-related side effects commonly reported in participants. There are 22 questions which comprise 5 scales (dysphagia, pain, reflux symptom, dietary restrictions, and anxiety) and 4 single items (dry mouth, hair loss, taste, body image). Most questions use 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms. Change of >=10 points has been found to be clinically significant. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.	Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months)
Secondary	Percentage of Participants With Advanced Gastric Cancer (AGC) Symptom Progression - Phase 3	AGC symptomatic progression: a worsening of >=10-points in any 1 of the abdominal discomfort, loss of appetite, weakness and fatigue, upper abdominal pain, change in bowel movement, and/or weight loss scales of the EORTC QLQ-C30 and QLQ-STO22. QLQ-STO22 supplements EORTC QLQ-C30 to assess symptoms and commonly reported treatment-related side effects. There are 22 questions comprise 5 scales (dysphagia, pain, reflux symptom, diet restrictions, anxiety), 4 single items (dry mouth, hair loss, taste, body image), which are related to the symptoms of the disease. Most questions used 4-point scale (1 'Not at all' to 4 'Very much'). All scores and single-items transformed to a scale of 0-100; higher score=better level of functioning or greater degree of symptoms. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.	Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months)
Secondary	Time to Advanced Gastric Cancer (AGC) Symptom Progression - Phase 3	Time to AGC symptom were defined as the time from randomization to the first documentation of an increase in at least one of the pre-specified abdominal discomfort, loss of appetite, weakness and fatigue, upper abdominal pain, change in bowel movement, and weight loss subscales of the QLQ STO22 and EORTC QLQ-C30. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.	Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months)
Secondary	Maximum Observed Plasma Concentration (Cmax) of Trastuzumab Emtansine (T-DM1) and Total Trastuzumab - Stage 1	Maximum observed plasma concentration of Trastuzumab Emtansine (T-DM1) and total trastuzumab were reported. Stage 1 consists of all participants recruited before the regimen selection, which was carried out after 12 weeks of randomization.	Day 1 (D1) of Cycle 1 (C1) and C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Secondary	Maximum Observed Plasma Concentration (Cmax) of N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) - Stage 1	Maximum observed plasma concentration of DM1 were reported. Stage 1 consists of all participants recruited before the regimen selection decision. Regimen selection analysis was carried out after 12 weeks of randomization.	C1D1 and C1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Secondary	Maximum Observed Plasma Concentration (Cmax) of Trastuzumab Emtansine (T-DM1) and Total Trastuzumab - Stage 2	Stage 2 consists of all participants recruited after the regimen selection decision up to primary data cut-off date 30-June-2015.	C1D1; C4D1
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] - Stage 1	AUCinf= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). Stage 1 consists of all participants recruited before the regimen selection decision. Regimen selection analysis was carried out after 12 weeks of randomization.	D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Secondary	Plasma Decay Half-Life (t1/2) - Stage 1	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Stage 1 consists of all participants recruited before the regimen selection decision. Regimen selection analysis was carried out after 12 weeks of randomization.	D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Secondary	Volume of Distribution at Steady State (Vss) - Stage 1	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Stage 1 consists of all participants recruited before the regimen selection decision. Regimen selection analysis was carried out after 12 weeks of randomization.	D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Secondary	Systemic Clearance (CL) - Stage 1	CL is a quantitative measure of the rate at which a drug substance is removed from the body. Stage 1 consists of all participants recruited before the regimen selection decision. Regimen selection analysis was carried out after 12 weeks of randomization.	D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)