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

NCT ID: NCT01641939

Last Updated: 2017-05-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 415 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-03
• Study Completion Date: 2016-04-30

Brief 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.

Conditions

Gastric Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Taxane

Intervention Type: DRUG

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 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.

Group Type: EXPERIMENTAL

trastuzumab emtansine

Intervention Type: DRUG

trastuzumab emtansine 2.4 mg/kg IV once a week

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.

Group Type: EXPERIMENTAL

trastuzumab emtansine

Intervention Type: DRUG

trastuzumab emtansine 3.6 mg/kg IV every 3 weeks

Interventions

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.

Intervention Type: DRUG

trastuzumab emtansine

trastuzumab emtansine 3.6 mg/kg IV every 3 weeks

Intervention Type: DRUG

trastuzumab emtansine

trastuzumab emtansine 2.4 mg/kg IV once a week

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Comprehensive Blood/Cancer Ctr

Bakersfield, California, United States

Stanford University School of Medicine

Stanford, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

University of Kansas; Medical Center & Medical pavilion

Westwood, Kansas, United States

Norton Healthcare Inc.

Louisville, Kentucky, United States

Massachusetts General Hospital.

Boston, Massachusetts, United States

Dana Farber Can Ins

Boston, Massachusetts, United States

Weill Cornell Medical College

New York, New York, United States

Vanderbilt

Nashville, Tennessee, United States

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Fundación Investigar

Buenos Aires, , Argentina

Hospital de Gastroenterologia Dr. Bonorino Udaondo ; Servicio de Oncología

Buenos Aires, , Argentina

Instituto de Oncología de Rosario

Rosario, , Argentina

UZ Leuven Gasthuisberg

Leuven, , Belgium

Instituto Nacional de Cancer - INCa; Oncologia

Rio de Janeiro, Rio de Janeiro, Brazil

Clinica de Oncologia de Porto Alegre - CliniOnco

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de Cancer de Barretos

Barretos, São Paulo, Brazil

Hospital Amaral Carvalho

Jaú, São Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

Instituto de Oncologia de Sorocaba - CEPOS

Sorocaba, São Paulo, Brazil

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Brampton Memorial Hospital, William Osler Health Center

Brampton, Ontario, Canada

Toronto East General Hospital; Haematology/Oncology

Toronto, Ontario, Canada

St. Michael'S Hospital

Toronto, Ontario, Canada

The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)

Beijing, , China

Beijing Cancer Hospital

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

Zhongshan Hospital Fudan University

Shanghai, , China

Shanghai First People's Hospital

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, , China

Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology

Hradec Králové, , Czechia

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, , Czechia

Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika

Prague, , Czechia

Fakultní Nemocnice V Motole; Radioterapeuticko-Onkologicke Oddeleni

Prague, , Czechia

Tampere University Hospital; Dept of Oncology

Tampere, , Finland

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

Hopital Saint Antoine; Hepatologie-Gastr-Enterologie

Paris, , France

Hop Europeen Georges Pompidou; Gastro Enterologie

Paris, , France

Hopital Robert Debre; Gastro Enterologie

Reims, , France

Hopital Purpan; Unite Onco Digestive

Toulouse, , France

Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.

Berlin, , Germany

Universitätsklinikum Köln

Cologne, , Germany

Universitätsklinikum "Carl Gustav Carus"; Med. Klinik & Poliklinik I, Arbeitsgr. intern. Onkologie

Dresden, , Germany

Facharztzentrum Eppendorf, Studien GbR

Hamburg, , Germany

Tagesklinik Landshut; Hämatologie/Onkologie

Landshut, , Germany

Onkologische Gemeinschaftspraxis

Magdeburg, , Germany

Centro Oncológico Sixtino / Centro Oncológico SA

Guatemala City, , Guatemala

Grupo Angeles

Guatemala City, , Guatemala

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, , Hungary

Campus Universitario S.Venuta; Centro Oncologico T.Campanella

Catanzaro, Calabria, Italy

AZ.Osp S. Orsola - Malpighi-Reparto di Oncologia Medica

Bologna, Emilia-Romagna, Italy

A.O. Città della Salute e della Scienza - Presidio Molinette; divisione oncologia medica

Turin, Piedmont, Italy

Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1

Florence, Tuscany, Italy

A.O. Universitaria Pisana; Oncologia

Pisa, Tuscany, Italy

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 College Of Medicine; Upper Gastroenterology

Hyōgo, , Japan

Hyogo Cancer Center; Gastroenterology

Hyōgo, , Japan

Ibaraki Prefectural Central Hospital; Gastroenterology

Ibaraki, , Japan

Tohoku Uni Hospital; Clinical Oncology

Miyagi, , Japan

Osaka University Hospital; Surgery

Osaka, , Japan

Kindai University Hospital; Medical Oncology

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

Toranomon Hospital; Medical Oncology

Tokyo, , Japan

Tokyo Metropolitan Komagome Hospital; Chemotherapy

Tokyo, , Japan

The Cancer Institute Hospital, JFCR; Gastroenterology

Tokyo, , Japan

Hospital Wanita dan Kanak-Kanak Sabah

Sabah, Sabah, Malaysia

University Malaya Medical Centre; Clinical Oncology Unit,

Kuala Lumpur, , Malaysia

Centenario Hospital Miguel Hidalgo

Aguascalientes, , Mexico

Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre

Chihuahua City, , Mexico

Hospital General de México; Unidad de Oncologia

Mexico City, , Mexico

Centro Hemato Oncologico Paitilla

Panama City, , Panama

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, , Peru

Perpetual Succour Hospital

Cebu, , Philippines

Veterans Memorial Medical Ctr; Cancer Research Centre

Quezon City, Luzon, , Philippines

Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii

Gdansk, , Poland

Szpital Uniwersytecki w Krakowie

Krakow, , Poland

Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie

Poznan, , Poland

Wojewódzki Szpital Specjalistyczny Nr 3

Rybnik, , Poland

Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie; Klinika Gastroenterologii Onkologicznej

Warsaw, , Poland

Institutul Clinic Fundeni Bucuresti

Bucharest, , Romania

Spitalul Universitar CF Cluj-Napoca; Sectia Oncologie

Cluj-Napoca, , Romania

Medisprof SRL

Cluj-Napoca, , Romania

Spitalul Clinic Judetean Mures; Oncologie Medicala

Târgu Mureş, , Romania

Arkhangelsk Regional Clinical Oncology Dispensary

Arkhangelsk, , Russia

Ivanovo Regional Oncology Dispensary

Ivanovo, , Russia

Omsk Region Clinical Oncology Dispensary; 1St Sergical Department

Omsk, , Russia

State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary

Pyatigorsk, , Russia

Tula Regional Oncology Dispensary

Tula, , Russia

National Cancer Centre

Singapore, , Singapore

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center; Medical Oncology

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Yonsei University Severance Hospital; Medical Oncology

Seoul, , South Korea

Korea University Anam Hospital; Oncology Haemotology

Seoul, , South Korea

Seoul St.Mary's Hospital; Medical Oncology

Seoul, , South Korea

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 Univ. Central de Asturias; Servicio de Oncologia

Oviedo, Principality of Asturias, 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 Universitario Virgen del Rocio; Servicio de Oncologia

Seville, , Spain

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, , Spain

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 District, , Taiwan

Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department

Erzurum, , Turkey (Türkiye)

Istanbul Bilim University School Of Medicine; Department Of Medical Oncology

Istanbul, , Turkey (Türkiye)

Marmara Uni Faculty of Medicine; Medical Oncology

Istanbul, , Turkey (Türkiye)

Ege Uni Medical Faculty; Oncology Dept

Izmir, , Turkey (Türkiye)

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

Sıhhiye, Ankara, , Turkey (Türkiye)

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 Kingdom

Countries

United States; Argentina; Belgium; Brazil; Canada; China; Czechia; Finland; France; Germany; Guatemala; Hungary; Italy; Japan; Malaysia; Mexico; Panama; Peru; Philippines; Poland; Romania; Russia; Singapore; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30706247 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28343975 (View on PubMed)

Other Identifiers

2012-000660-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO27952

Identifier Type: -

Identifier Source: org_study_id