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

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

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.

Study Overview

• Status: Terminated
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Taxane; Drug: trastuzumab emtansine; Drug: trastuzumab emtansine

• Study Type: Interventional
• Enrollment (Actual): 415
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1025
    • Fundación Investigar
  • Buenos Aires, Argentina, C1264AAA
    • Hospital de Gastroenterologia Dr. Bonorino Udaondo ; Servicio de Oncología
  • Rosario, Argentina, S2000KZE
    • Instituto de Oncología de Rosario
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20560-120
      • Instituto Nacional de Cancer - INCa; Oncologia
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
    • Porto Alegre, RS, Brazil, 90430-090
      • Clinica de Oncologia de Porto Alegre - CliniOnco
  • SP
    • Barretos, SP, Brazil, 14784-400
      • Hospital de Cancer de Barretos
    • Jau, SP, Brazil, 17210-080
      • Hospital Amaral Carvalho
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
    • Sorocaba, SP, Brazil, 18030-245
      • Instituto de Oncologia de Sorocaba - CEPOS
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Brampton Memorial Hospital, William Osler Health Center
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M4C 3E7
      • Toronto East General Hospital; Haematology/Oncology
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100071
    • The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Changchun, China, 130012
    • Jilin Cancer Hospital
  • Changzhou, China, 213003
    • Changzhou First People's Hospital
  • ChongQing, China, 400042
    • Third Affiliated Hospital of Third Military Medical University
  • Fuzhou, China, 350014
    • Fujian cancer hospital
  • Guangzhou, China, 510060
    • Sun Yet-sen University Cancer Center
  • Hangzhou, China, 310016
    • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Nanjing, China, 210009
    • Jiangsu Cancer Hospital
  • Nanjing, China
    • The 81st Hospital of P.L.A.
  • Nantong, China, 226001
    • Affiliated Hospital Of Nantong University
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
  • Shanghai, China, 200080
    • Shanghai First People's Hospital
  • Shenyang, China, 110016
    • General Hospital of Shenyang Military Command of PLA
  • Wuhan, China, 430023
    • Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
  • Xuzhou, China, 221004
    • The Affiliated Hospital of Xuzhou Medical College
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc; Onkologicka klinika
  • Praha 2, Czechia, 128 08
    • Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika
  • Praha 5, Czechia, 150 06
    • Fakultní Nemocnice V Motole; Radioterapeuticko-Onkologicke Oddeleni
• Finland
  • Tampere, Finland, 33520
    • Tampere University Hospital; Dept of Oncology
• France
  • Brest, France, 29200
    • Hopital Augustin Morvan; Federation De Cancerologie
  • Clichy, France, 92118
    • Hopital Beaujon; Gastro Enterologie 1
  • Montpellier, France, 34298
    • Centre Val Aurelle Paul Lamarque; Medecine A1 A2
  • Paris, France, 75571
    • Hopital Saint Antoine; Hepatologie-Gastr-Enterologie
  • Paris, France, 75908
    • Hop Europeen Georges Pompidou; Gastro Enterologie
  • Reims, France, 51092
    • Hopital Robert Debre; Gastro Enterologie
  • Toulouse, France, 31059
    • Hopital Purpan; Unite Onco Digestive
• Germany
  • Berlin, Germany, 10117
    • Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus"; Med. Klinik & Poliklinik I, Arbeitsgr. intern. Onkologie
  • Hamburg, Germany, 20249
    • Facharztzentrum Eppendorf, Studien GbR
  • Köln, Germany, 50937
    • Universitatsklinikum Koln
  • Landshut, Germany, 84028
    • Tagesklinik Landshut; Hämatologie/Onkologie
  • Magdeburg, Germany, 39104
    • Onkologische Gemeinschaftspraxis
• Guatemala
  • Guatemala, Guatemala, 01010
    • Centro Oncológico Sixtino / Centro Oncológico SA
  • Guatemala City, Guatemala, 01015
    • Grupo Angeles
• Hungary
  • Budapest, Hungary, 1097
    • Fovarosi Szent Laszlo Korhaz-Rendelointezet; Onkologiai Osztaly X
  • Szeged, Hungary, 6720
    • Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika
  • Szolnok, Hungary, 5004
    • Hetenyi Geza County Hospital; Onkologiai Kozpont
  • Zalaegerszeg, Hungary, 8900
    • Zala Megyei Kórház, Külsö Kórház, Pózva; Onkológiai Osztály
• Italy
  • Calabria
    • Catanzaro, Calabria, Italy, 88100
      • Campus Universitario S.Venuta; Centro Oncologico T.Campanella
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • AZ.Osp S. Orsola - Malpighi-Reparto di Oncologia Medica
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • A.O. Città della Salute e della Scienza - Presidio Molinette; divisione oncologia medica
  • Toscana
    • Firenze, Toscana, Italy, 50139
      • Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1
    • Pisa, Toscana, Italy, 56100
      • A.O. Universitaria Pisana; Oncologia
• Japan
  • Aichi, Japan, 464-8681
    • Aichi Cancer Center Hospital; Clinical Oncology
  • Chiba, Japan, 260-8717
    • Chiba Cancer Center; Gastroenterology
  • Chiba, Japan, 277-8577
    • National Cancer Center Hospital East; Gastroenterology
  • Ehime, Japan, 791-0280
    • National Hospital Organization Shikoku Cancer Center; Gastroenterology
  • Hokkaido, Japan, 060-8648
    • Hokkaido University Hospital：Gastroenterology
  • Hyogo, Japan, 663-8501
    • Hyogo College Of Medicine; Upper Gastroenterology
  • Hyogo, Japan, 673-8558
    • Hyogo Cancer Center; Gastroenterology
  • Ibaraki, Japan, 309-1793
    • Ibaraki Prefectural Central Hospital; Gastroenterology
  • Miyagi, Japan, 980-8574
    • Tohoku Uni Hospital; Clinical Oncology
  • Osaka, Japan, 565-0871
    • Osaka University Hospital; Surgery
  • Osaka, Japan, 589-8511
    • Kindai University Hospital; Medical Oncology
  • Saitama, Japan, 362-0806
    • Saitama Cancer Center; Gastroenterology
  • Shizuoka, Japan, 411-8777
    • Shizuoka Cancer Center; Gastroenterology
  • Shizuoka, Japan, 420-8527
    • Shizuoka General Hospital; Clinical Oncology
  • Tochigi, Japan, 320-0834
    • Tochigi Cancer Center; Medical Oncology
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital; Gastrointestinal Oncology
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital; Medical Oncology
  • Tokyo, Japan, 113-8677
    • Tokyo Metropolitan Komagome Hospital; Chemotherapy
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital, JFCR; Gastroenterology
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Severance Hospital; Medical Oncology
  • Seoul, Korea, Republic of, 136-705
    • Korea University Anam Hospital; Oncology Haemotology
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center; Medical Oncology
  • Seoul, Korea, Republic of, 137-807
    • Seoul St.Mary's Hospital; Medical Oncology
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre; Clinical Oncology Unit,
  • Sabah, Malaysia, 88996
    • Hospital Wanita Dan Kanak-kanak Sabah
• Mexico
  • Aguascalientes, Mexico, 20230
    • Centenario Hospital Miguel Hidalgo
  • Chihuahua, Mexico, 31000
    • Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre
  • Mexico DF, Mexico, 06726
    • Hospital General de México; Unidad de Oncologia
• Panama
  • Panama City, Panama, 083200752
    • Centro Hemato Oncologico Paitilla
• Peru
  • Chiclayo, Peru, CIX
    • Hospital Nacional Almanzor Aguinaga Asenjo; Unidad De Investigacion Del Servicio De Oncologia Medica
  • Cusco, Peru, 08006
    • Hospital Nacional Adolfo Guevara Velasco
  • Jesus Maria, Peru, Lima 11
    • Hospital Nacional Edgardo Rebagliati Martins
  • Lima, Peru, 34
    • Instituto Nacional de Enfermedades Neoplasicas
• Philippines
  • Cebu, Philippines, 6000
    • Perpetual Succour Hospital
  • Quezon City, Luzon, Philippines, 1101
    • Veterans Memorial Medical Ctr; Cancer Research Centre
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
  • Krakow, Poland, 31-501
    • Szpital Uniwersytecki w Krakowie
  • Poznan, Poland, 61-866
    • Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie
  • Rybnik, Poland, 44-200
    • Wojewódzki Szpital Specjalistyczny Nr 3
  • Warszawa, Poland, 02-781
    • Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie; Klinika Gastroenterologii Onkologicznej
• Romania
  • Bucharest, Romania, 022328
    • Institutul Clinic Fundeni Bucuresti
  • Cluj-Napoca, Romania, 400015
    • Spitalul Universitar CF Cluj-Napoca; Sectia Oncologie
  • Cluj-Napoca, Romania, 400058
    • Medisprof srl
  • Targu Mures, Romania, 540141
    • Spitalul Clinic Judetean Mures; Oncologie Medicala
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Arkhangelsk Regional Clinical Oncology Dispensary
  • Ivanovo, Russian Federation, 153040
    • Ivanovo Regional Oncology Dispensary
  • Omsk, Russian Federation, 644013
    • Omsk Region Clinical Oncology Dispensary; 1St Sergical Department
  • Pyatigorsk, Russian Federation, 357502
    • State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary
  • Tula, Russian Federation, 300053
    • Tula Regional Oncology Dispensary
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Farmacia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de Oncologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet; Servicio Oncologia
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Univ. Central de Asturias; Servicio de Oncologia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla; Servicio de Oncologia
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
• Taiwan
  • Kaohsung, Taiwan, 883
    • Kaohsiung Chang Gung Memorial Hospital; Dept of Hem and Onc
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital; Dept of Oncology
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology
• Turkey
  • Erzurum, Turkey, 25240
    • Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department
  • Istanbul, Turkey, 34890
    • Marmara Uni Faculty of Medicine; Medical Oncology
  • Istanbul, Turkey, 34300
    • Istanbul Bilim University School Of Medicine; Department Of Medical Oncology
  • Izmir, Turkey, 35100
    • Ege Uni Medical Faculty; Oncology Dept
  • Sıhhiye, ANKARA, Turkey, 06100
    • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Centre; Oncology Dept
  • Glasgow, United Kingdom, G12 0YN
    • The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital; Dept of Med-Onc
  • Manchester, United Kingdom, M2O 4BX
    • Christie Hospital Nhs Trust; Medical Oncology
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital; Dept of Medical Oncology
  • Weston Super Mare, United Kingdom, BS23 4TQ
    • BRISTOL ONCOLOGY CENTRE; CLINICAL TRIALS UNIT; R & D department
• United States
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood/Cancer Ctr
    • Stanford, California, United States, 94305-5151
      • Stanford University School of Medicine
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas; Medical Center & Medical pavilion
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Healthcare Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Can Ins
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital.
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard taxane therapy; Docetaxel will be administered at 75 milligram per meter square (mg/m^2) intravenous (IV) on Day 1 of a 21-day cycle, or paclitaxel will administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) according to investigator choice until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.	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.
Experimental: trastuzumab emtansine 2.4 mg; Trastuzumab emtansine will be administered on Day 1, 8, and 15 of a 21-day cycle at 2.4 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.	Drug: trastuzumab emtansine; trastuzumab emtansine 3.6 mg/kg IV every 3 weeks; Drug: trastuzumab emtansine; trastuzumab emtansine 2.4 mg/kg IV once a week
Experimental: trastuzumab emtansine 3.6 mg; Trastuzumab emtansine will be administered on Day 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.	Drug: trastuzumab emtansine; trastuzumab emtansine 3.6 mg/kg IV every 3 weeks; Drug: trastuzumab emtansine; trastuzumab emtansine 2.4 mg/kg IV once a week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Shah MA, Kang YK, Thuss-Patience PC, Ohtsu A, Ajani JA, Van Cutsem E, Hoersch S, Harle-Yge ML, de Haas SL. Biomarker analysis of the GATSBY study of trastuzumab emtansine versus a taxane in previously treated HER2-positive advanced gastric/gastroesophageal junction cancer. Gastric Cancer. 2019 Jul;22(4):803-816. doi: 10.1007/s10120-018-00923-7. Epub 2019 Jan 31.
• Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. doi: 10.1016/S1470-2045(17)30111-0. Epub 2017 Mar 23.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2012
• Primary Completion (Actual): June 30, 2015
• Study Completion (Actual): April 30, 2016

Study Registration Dates

• First Submitted: July 13, 2012
• First Submitted That Met QC Criteria: July 13, 2012
• First Posted (Estimate): July 17, 2012

Study Record Updates

• Last Update Posted (Actual): May 12, 2017
• Last Update Submitted That Met QC Criteria: May 5, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Trastuzumab; Maytansine; Taxane; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: BO27952; 2012-000660-22 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No