MedPath

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

Phase 2
Terminated
Conditions
Gastric Cancer
Interventions
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
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.
Read More
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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Standard taxane therapyTaxaneDocetaxel 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 mgtrastuzumab emtansineTrastuzumab 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 mgtrastuzumab emtansineTrastuzumab 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
NameTimeMethod
Overall Survival (OS)- Phase 3Date 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
NameTimeMethod
Percentage of Participants With Disease Progression or Death According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1) - Phase 3Date 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 3Day 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 3Day 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 1Day 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 3Date 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 3Day 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 3Day 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 3Date 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 3Date 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 1D1C1 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 1D1C1 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 1D1C1 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 1C1D1 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 2C1D1; 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 1D1C1 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

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