A Study of Trastuzumab Emtansine Versus Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer
- Registration Number
- NCT01641939
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 415
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard taxane therapy Taxane 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. trastuzumab emtansine 3.6 mg trastuzumab emtansine 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. trastuzumab emtansine 2.4 mg trastuzumab emtansine 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS)- Phase 3 Date of randomization until death (up to 2 years 3 months) 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).
Overall Survival (OS) - Phase 2 (Dose Selection Portion of the Study) Date of randomization until death (up to 1 year) 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Disease Progression or Death According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1) - Phase 3 Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months) 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.
Percentage of Participants With Advanced Gastric Cancer (AGC) Symptom Progression - Phase 3 Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months) 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.
Time to Advanced Gastric Cancer (AGC) Symptom Progression - Phase 3 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 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.
Maximum Observed Plasma Concentration (Cmax) of Trastuzumab Emtansine (T-DM1) and Total Trastuzumab - Stage 1 Day 1 (D1) of Cycle 1 (C1) and C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) 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.
Duration of Objective Response (DOR) - Phase 3 Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months) 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.
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 Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at follow-up (up to 2 years 3 months) 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.
Percentage of Participants With Clinically Significant Improvement in Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22) Score - Phase 3 Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months) 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.
Percentage of Participants With Objective Response According to mRECIST v1.1 - Phase 3 Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months) 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.
Progression Free Survival (PFS) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1) - Phase 3 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 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).
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] - Stage 1 D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) 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.
Plasma Decay Half-Life (t1/2) - Stage 1 D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) 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.
Volume of Distribution at Steady State (Vss) - Stage 1 D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) 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.
Maximum Observed Plasma Concentration (Cmax) of N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) - Stage 1 C1D1 and C1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) 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.
Maximum Observed Plasma Concentration (Cmax) of Trastuzumab Emtansine (T-DM1) and Total Trastuzumab - Stage 2 C1D1; C4D1 Stage 2 consists of all participants recruited after the regimen selection decision up to primary data cut-off date 30-June-2015.
Systemic Clearance (CL) - Stage 1 D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks) 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.
Trial Locations
- Locations (148)
Centro Oncológico Sixtino / Centro Oncológico SA
🇬🇹Guatemala, Guatemala
Centenario Hospital Miguel Hidalgo
🇲🇽Aguascalientes, Mexico
Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre
🇲🇽Chihuahua, Mexico
Spitalul Universitar CF Cluj-Napoca; Sectia Oncologie
🇷🇴Cluj-Napoca, Romania
National Taiwan Uni Hospital; Dept of Oncology
🇨🇳Taipei, Taiwan
Grupo Angeles
🇬🇹Guatemala City, Guatemala
Centro Hemato Oncologico Paitilla
🇵🇦Panama City, Panama
Medisprof SRL
🇷🇴Cluj-Napoca, Romania
Spitalul Clinic Judetean Mures; Oncologie Medicala
🇷🇴Targu Mures, Romania
Hospital Nacional Adolfo Guevara Velasco
🇵🇪Cusco, Peru
National Cancer Centre
🇸🇬Singapore, Singapore
Campus Universitario S.Venuta; Centro Oncologico T.Campanella
🇮🇹Catanzaro, Calabria, Italy
Hospital Univ. Central de Asturias; Servicio de Oncologia
🇪🇸Oviedo, Asturias, Spain
Kaohsiung Chang Gung Memorial Hospital; Dept of Hem and Onc
🇨🇳Kaohsung, Taiwan
Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology
🇨🇳Taoyuan, Taiwan
Third Affiliated Hospital of Third Military Medical University
🇨🇳ChongQing, China
Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center
🇨🇳Wuhan, China
Hopital Robert Debre; Gastro Enterologie
🇫🇷Reims, France
Brampton Memorial Hospital, William Osler Health Center
🇨🇦Brampton, Ontario, Canada
Toronto East General Hospital; Haematology/Oncology
🇨🇦Toronto, Ontario, Canada
Stanford University School of Medicine
🇺🇸Stanford, California, United States
University of Kansas; Medical Center & Medical pavilion
🇺🇸Westwood, Kansas, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Comprehensive Blood/Cancer Ctr
🇺🇸Bakersfield, California, United States
Norton Healthcare Inc.
🇺🇸Louisville, Kentucky, United States
Vanderbilt
🇺🇸Nashville, Tennessee, United States
Clinica de Oncologia de Porto Alegre - CliniOnco
🇧🇷Porto Alegre, RS, Brazil
Instituto de Oncologia de Sorocaba - CEPOS
🇧🇷Sorocaba, SP, Brazil
BCCA-Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
Beijing Cancer Hospital
🇨🇳Beijing, China
The Affiliated Hospital of Xuzhou Medical College
🇨🇳Xuzhou, China
Tampere University Hospital; Dept of Oncology
🇫🇮Tampere, Finland
A.O. Universitaria Pisana; Oncologia
🇮🇹Pisa, Toscana, Italy
Hyogo College Of Medicine; Upper Gastroenterology
🇯🇵Hyogo, Japan
Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika
🇨🇿Praha 2, Czechia
A.O. Città della Salute e della Scienza - Presidio Molinette; divisione oncologia medica
🇮🇹Torino, Piemonte, Italy
AZ.Osp S. Orsola - Malpighi-Reparto di Oncologia Medica
🇮🇹Bologna, Emilia-Romagna, Italy
Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1
🇮🇹Firenze, Toscana, Italy
Hop Europeen Georges Pompidou; Gastro Enterologie
🇫🇷Paris, France
Fakultní Nemocnice V Motole; Radioterapeuticko-Onkologicke Oddeleni
🇨🇿Praha 5, Czechia
Centre Val Aurelle Paul Lamarque; Medecine A1 A2
🇫🇷Montpellier, France
Kindai University Hospital; Medical Oncology
🇯🇵Osaka, Japan
Saitama Cancer Center; Gastroenterology
🇯🇵Saitama, Japan
Shizuoka General Hospital; Clinical Oncology
🇯🇵Shizuoka, Japan
National Cancer Center Hospital; Gastrointestinal Oncology
🇯🇵Tokyo, Japan
Toranomon Hospital; Medical Oncology
🇯🇵Tokyo, Japan
Tokyo Metropolitan Komagome Hospital; Chemotherapy
🇯🇵Tokyo, Japan
Istanbul Bilim University School Of Medicine; Department Of Medical Oncology
🇹🇷Istanbul, Turkey
Velindre Cancer Centre; Oncology Dept
🇬🇧Cardiff, United Kingdom
The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit
🇬🇧Glasgow, United Kingdom
Hospital Wanita dan Kanak-Kanak Sabah
🇲🇾Sabah, Malaysia
Hospital General de México; Unidad de Oncologia
🇲🇽Mexico DF, Mexico
Hospital Nacional Almanzor Aguinaga Asenjo; Unidad De Investigacion Del Servicio De Oncologia Medica
🇵🇪Chiclayo, Peru
Instituto Nacional de Enfermedades Neoplasicas
🇵🇪Lima, Peru
Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie
🇵🇱Poznan, Poland
Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
🇵🇱Gdansk, Poland
Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Institutul Clinic Fundeni Bucuresti
🇷🇴Bucharest, Romania
Wojewódzki Szpital Specjalistyczny Nr 3
🇵🇱Rybnik, Poland
Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie; Klinika Gastroenterologii Onkologicznej
🇵🇱Warszawa, Poland
Hospital Clinic i Provincial; Servicio de Farmacia
🇪🇸Barcelona, Spain
BRISTOL ONCOLOGY CENTRE; CLINICAL TRIALS UNIT; R & D department
🇬🇧Weston Super Mare, United Kingdom
Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
🇪🇸Santiago de Compostela, La Coruña, Spain
Hospital Universitario Miguel Servet; Servicio Oncologia
🇪🇸Zaragoza, Spain
Christie Hospital Nhs Trust; Medical Oncology
🇬🇧Manchester, United Kingdom
Shizuoka Cancer Center; Gastroenterology
🇯🇵Shizuoka, Japan
Tochigi Cancer Center; Medical Oncology
🇯🇵Tochigi, Japan
Yonsei University Severance Hospital; Medical Oncology
🇰🇷Seoul, Korea, Republic of
Arkhangelsk Regional Clinical Oncology Dispensary
🇷🇺Arkhangelsk, Russian Federation
Universitätsklinikum Köln
🇩🇪Köln, Germany
Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
🇩🇪Berlin, Germany
Tagesklinik Landshut; Hämatologie/Onkologie
🇩🇪Landshut, Germany
Facharztzentrum Eppendorf, Studien GbR
🇩🇪Hamburg, Germany
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, SP, Brazil
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Massachusetts General Hospital.
🇺🇸Boston, Massachusetts, United States
Dana Farber Can Ins
🇺🇸Boston, Massachusetts, United States
University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Hospital de Gastroenterologia Dr. Bonorino Udaondo ; Servicio de Oncología
🇦🇷Buenos Aires, Argentina
Fundación Investigar
🇦🇷Buenos Aires, Argentina
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Instituto de Oncología de Rosario
🇦🇷Rosario, Argentina
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, RS, Brazil
Instituto Nacional de Cancer - INCa; Oncologia
🇧🇷Rio de Janeiro, RJ, Brazil
Hospital Amaral Carvalho
🇧🇷Jau, SP, Brazil
Hospital de Cancer de Barretos
🇧🇷Barretos, SP, Brazil
the First Hospital of Jilin University
🇨🇳Changchun, China
Jilin Cancer Hospital
🇨🇳Changchun, China
St. Michael'S Hospital
🇨🇦Toronto, Ontario, Canada
Changzhou First People's Hospital
🇨🇳Changzhou, China
The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)
🇨🇳Beijing, 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
Affiliated Hospital of Nantong University
🇨🇳Nantong, China
General Hospital of Shenyang Military Command of PLA
🇨🇳Shenyang, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
🇨🇳Xi'an, China
Shanghai First People's Hospital
🇨🇳Shanghai, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology
🇨🇿Hradec Kralove, Czechia
Fakultni nemocnice Olomouc; Onkologicka klinika
🇨🇿Olomouc, Czechia
Hopital Beaujon; Gastro Enterologie 1
🇫🇷Clichy, France
Hopital Augustin Morvan; Federation De Cancerologie
🇫🇷Brest, France
Hopital Purpan; Unite Onco Digestive
🇫🇷Toulouse, France
Hopital Saint Antoine; Hepatologie-Gastr-Enterologie
🇫🇷Paris, France
Universitätsklinikum "Carl Gustav Carus"; Med. Klinik & Poliklinik I, Arbeitsgr. intern. Onkologie
🇩🇪Dresden, Germany
Onkologische Gemeinschaftspraxis
🇩🇪Magdeburg, Germany
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
Hokkaido University Hospital:Gastroenterology
🇯🇵Hokkaido, Japan
Hyogo Cancer Center; Gastroenterology
🇯🇵Hyogo, Japan
Chiba Cancer Center; Gastroenterology
🇯🇵Chiba, Japan
Aichi Cancer Center Hospital; Clinical Oncology
🇯🇵Aichi, Japan
National Hospital Organization Shikoku Cancer Center; Gastroenterology
🇯🇵Ehime, Japan
National Cancer Center Hospital East; Gastroenterology
🇯🇵Chiba, Japan
Ibaraki Prefectural Central Hospital; Gastroenterology
🇯🇵Ibaraki, Japan
Osaka University Hospital; Surgery
🇯🇵Osaka, Japan
Tohoku Uni Hospital; Clinical Oncology
🇯🇵Miyagi, Japan
The Cancer Institute Hospital, JFCR; Gastroenterology
🇯🇵Tokyo, Japan
Asan Medical Center; Medical Oncology
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
University Malaya Medical Centre; Clinical Oncology Unit,
🇲🇾Kuala Lumpur, Malaysia
Seoul St.Mary's Hospital; Medical Oncology
🇰🇷Seoul, Korea, Republic of
Korea University Anam Hospital; Oncology Haemotology
🇰🇷Seoul, Korea, Republic of
Hospital Nacional Edgardo Rebagliati Martins
🇵🇪Jesus Maria, Peru
Veterans Memorial Medical Ctr; Cancer Research Centre
🇵🇭Quezon City, Luzon, Philippines
Perpetual Succour Hospital
🇵🇭Cebu, Philippines
Omsk Region Clinical Oncology Dispensary; 1St Sergical Department
🇷🇺Omsk, Russian Federation
Ivanovo Regional Oncology Dispensary
🇷🇺Ivanovo, Russian Federation
State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary
🇷🇺Pyatigorsk, Russian Federation
Tula Regional Oncology Dispensary
🇷🇺Tula, Russian Federation
Hospital Universitario Marques de Valdecilla; Servicio de Oncologia
🇪🇸Santander, Cantabria, Spain
Hospital Universitario La Paz; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
🇪🇸Sevilla, Spain
Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department
🇹🇷Erzurum, 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
🇹🇷Sıhhiye, ANKARA, Turkey
Royal Marsden Hospital; Dept of Med-Onc
🇬🇧London, United Kingdom
Royal Marsden Hospital; Dept of Medical Oncology
🇬🇧Sutton, United Kingdom
Jiangsu Cancer Hospital
🇨🇳Nanjing, China
The 81st Hospital of P.L.A.
🇨🇳Nanjing, China
Fujian Cancer Hospital
🇨🇳Fuzhou, China