MedPath

A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer

Phase 3
Active, not recruiting
Conditions
HER2-positive Breast Cancer
Interventions
Registration Number
NCT03975647
Lead Sponsor
Seagen, a wholly owned subsidiary of Pfizer
Brief Summary

This study is being done to see if tucatinib with ado-trastuzumab emtansine (T-DM1) works better than T-DM1 alone to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery.

Patients in this study will be randomly assigned to get either tucatinib or placebo (a pill with no medicine). This is a blinded study, so neither patients nor their doctors will know whether a patient gets tucatinib or placebo. All patients in the study will get T-DM1, a drug that is often used to treat this cancer.

Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills or placebo pills two times every day. Patients will get T-DM1 injections from the study site staff on the first day of every cycle.

Detailed Description

This study is designed to evaluate the efficacy and safety of tucatinib in combination with T-DM1 in participants with unresectable locally-advanced or metastatic HER2+ breast cancer who have had prior treatment with a taxane and trastuzumab in any setting. Prior pertuzumab treatment is permitted, but not required. Participants will be randomized in a 1:1 manner to receive 21-day cycles of either tucatinib or placebo in combination with T-DM1.

While on study treatment, participants will be assessed for progression every 6 weeks for the first 24 weeks, and every 9 weeks thereafter, irrespective of dose holds or interruptions. Study treatment will continue until unacceptable toxicity, disease progression, withdrawal of consent, or study closure. After completion of study treatment and after occurrence of disease progression, participants in both arms of the study will continue to be followed for survival until study closure or withdrawal of consent.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
466
Inclusion Criteria
  • Histologically confirmed HER2+ breast carcinoma as determined by a sponsor-designated central laboratory
    • History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination

    • Have progression of unresectable locally advanced/metastatic breast cancer after last systemic therapy, or be intolerant of last systemic therapy

    • Measurable or non-measurable disease assessable by RECIST v1.1

    • ECOG performance status score of 0 or 1

    • CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must have at least one of the following:

      (a) No evidence of brain metastases

      (b) Untreated brain metastases not needing immediate local therapy

      (c) Previously treated brain metastases

      1. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy

      2. Participants treated with CNS local therapy for newly identified lesions or previously treated and progressing lesions may be eligible to enroll if all of the following criteria are met:

        (i) Time since SRS is at least 7 days prior to first dose of study treatment, time since WBRT is at least 14 days prior to first dose, or time since surgical resection is at least 28 days.

        (ii) Other sites of evaluable disease are present

      3. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions

Exclusion Criteria
  • Prior treatment with tucatinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity).
    • CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must not have any of the following:

      1. Any untreated brain lesions >2 cm in size
      2. Ongoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent).
      3. Any brain lesion thought to require immediate local therapy
      4. Known or concurrent leptomeningeal disease as documented by the investigator
      5. Poorly controlled generalized or complex partial seizures

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Tucatinib + T-DM1tucatinibTucatinib + T-DM1
Tucatinib + T-DM1T-DM1Tucatinib + T-DM1
Placebo + T-DM1placeboPlacebo + T-DM1
Placebo + T-DM1T-DM1Placebo + T-DM1
Primary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 Based on Investigator AssessmentFrom the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months)

PFS as per investigator was defined as the time from the date of randomization to the investigator assessment of disease progression (PD) as per RECIST v1.1 or death from any cause, whichever occurred first. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimiter (mm). Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)Up to approximately 5 years

OS was defined as the time from randomization to death due to any cause. For a participant who was not known to have died by the end of study follow-up, observation of OS was censored on the date the participant was last known to be alive (i.e., the date of last contact).

Progression-Free Survival as Per RECIST v1.1 in Participants With Brain Metastases at Baseline Based on Investigator AssessmentFrom the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 45 months)

PFS as per investigator was defined as the time from the date of randomization to the investigator assessment of PD as per RECIST v1.1 or death from any cause, whichever occurred first. PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. PFS was analyzed in participants with presence or history of brain metastases.

Objective Response Rate (ORR) as Per RECIST v1.1 Based on Investigator AssessmentFrom the date of first CR or PR until the date of the first documentation of PD or death, whichever occurred first (maximum up to 43 months)

ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (\<)10 mm. PR: a greater than equal (\>=) 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For a response to be considered as confirmed, the subsequent response needs to be at least 4 weeks after the initial response. ORR by investigator assessment is based on investigator response assessments. Two-sided 95% exact confidence interval, computed using the Clopper-Pearson method.

Progression-Free Survival as Per RECIST v1.1 Determined by Blinded Independent Committee Review (BICR)From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months)

PFS as per BICR was defined as the time from the date of randomization to the centrally-reviewed documented PD as per RECIST v1.1 or death from any cause, whichever occurred first. PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants without documented progression of PD or death at the time of analysis were censored at the date of the last tumor assessment.

Progression-Free Survival in Participants With Brain Metastases at Baseline as Per RECIST v1.1 Determined by BICRFrom the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months)

PFS as per BICR was defined as the time from the date of randomization to the centrally-reviewed documented PD as per RECIST v1.1 or death from any cause, whichever occurred first. PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PFS was analyzed in participants with presence or history of brain metastases.

Objective Response Rate as Per RECIST v1.1 Determined by BICRFrom the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months)

ORR was defined as the percentage of participants with confirmed CR or PR according to RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: A \>= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR per BICR is based on BICR response assessments.

Overall Survival in Participants With Brain Metastases at BaselineUp to approximately 5 years

OS was defined as the time from randomization to death due to any cause. For a participant who was not known to have died by the end of study follow-up, observation of OS was censored on the date the participant was last known to be alive (i.e., the date of last contact). OS was analyzed in participants with presence or history of brain metastases.

Duration of Response (DOR) as Per RECIST v1.1 Based on Investigator AssessmentUp to approximately 5 years

DOR was defined as the time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD as per RECIST v1.1 PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: A\>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DOR per investigator was based on investigator response assessments.

Duration of Response as Per RECIST v1.1 by BICRUp to approximately 5 years

DOR was defined as the time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD as per RECIST v1.1 PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: A\>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DOR per BICR was based on BICR response assessments.

Clinical Benefit Rate (CBR) Per RECIST v1.1 Based on Investigator AssessmentUp to approximately 5 years

CBR was defined as the percentage of participants with stable disease (SD) or non-CR or non-PD \>= 6 months or best response of CR or PR according to RECIST v1.1. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: A \>= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CBR was based on investigator assessment.

Clinical Benefit Rate as Per RECIST v1.1 by BICRUp to approximately 5 years

CBR was defined as the percentage of participants with SD or non-CR or non-PD \>= 6 months or best response of CR or PR according to RECIST v1.1. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: A \>= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CBR per BICR is based on BICR response assessments.

Number of Participants With Treatment Emergent Adverse Events (AEs)From start of treatment up to 30 days after the last study treatment (approximately 43 months)

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE was defined as AE that is newly occurred or worsened after the start of study treatment.

Trial Locations

Locations (272)

Texas Oncology - Medical City Dallas

🇺🇸

Dallas, Texas, United States

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Winship Cancer Institute / Emory University School of Medicine

🇺🇸

Atlanta, Georgia, United States

Mercy Medical Center -Weinberg Center

🇺🇸

Baltimore, Maryland, United States

Cancer Treatment Centers of America / Eastern Regional Medical Center

🇺🇸

Philadelphia, Pennsylvania, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

University of Chicago Medical Center

🇺🇸

Chicago, Illinois, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Swedish Cancer Institute

🇺🇸

Seattle, Washington, United States

Texas Oncology - Houston Memorial City

🇺🇸

Houston, Texas, United States

MD Anderson Cancer Center / University of Texas

🇺🇸

Houston, Texas, United States

Baylor Clinic

🇺🇸

Houston, Texas, United States

Oncology Consultants, PA

🇺🇸

Houston, Texas, United States

Miami Cancer Institute at Baptist Health, Inc.

🇺🇸

Miami, Florida, United States

Comprehensive Cancer Centers of Nevada

🇺🇸

Las Vegas, Nevada, United States

Minnesota Oncology Hematology P.A.

🇺🇸

Minneapolis, Minnesota, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Texas Oncology - San Antonio Medical Center

🇺🇸

San Antonio, Texas, United States

San Francisco General Hospital

🇺🇸

San Francisco, California, United States

University of California, San Francisco | HDFCCC - Hematopoietic Malignancies

🇺🇸

San Francisco, California, United States

Tennessee Oncology-Nashville/Sarah Cannon Research Institute

🇺🇸

Nashville, Tennessee, United States

Huntsman Cancer Institute/University of Utah

🇺🇸

Salt Lake City, Utah, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Arizona Oncology Associates, PC - HAL

🇺🇸

Phoenix, Arizona, United States

Cancer Centers of Colorado - Denver

🇺🇸

Denver, Colorado, United States

Providence Portland Medical Center

🇺🇸

Portland, Oregon, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

Nebraska Cancer Specialists

🇺🇸

Omaha, Nebraska, United States

University of California Davis

🇺🇸

Sacramento, California, United States

Rocky Mountain Cancer Centers - Aurora

🇺🇸

Aurora, Colorado, United States

University of Colorado Hospital / University of Colorado

🇺🇸

Aurora, Colorado, United States

H. Lee Moffitt Cancer Center and Research Institute

🇺🇸

Tampa, Florida, United States

American Oncology Networks LLC

🇺🇸

Bethesda, Maryland, United States

Banner MD Anderson Cancer Center

🇺🇸

Gilbert, Arizona, United States

Cancer Treatment Centers of America / Western Regional Medical Center

🇺🇸

Goodyear, Arizona, United States

Ironwood Cancer & Research Centers - Chandler

🇺🇸

Chandler, Arizona, United States

Arizona Oncology Associates, PC - HOPE

🇺🇸

Tucson, Arizona, United States

St. Bernards Medical Center

🇺🇸

Jonesboro, Arkansas, United States

St. Joseph Heritage Healthcare TRIO

🇺🇸

Fullerton, California, United States

California Cancer Associates for Research and Excellence Inc (cCARE)

🇺🇸

Encinitas, California, United States

City of Hope National Medical Center

🇺🇸

Duarte, California, United States

Chao Family Comprehensive Cancer Center University of California Irvine

🇺🇸

Orange, California, United States

University of California Irvine - Newport

🇺🇸

Orange, California, United States

Kaiser Permanente Medical Center Northern California

🇺🇸

Vallejo, California, United States

University of Colorado Health Memorial Hospital

🇺🇸

Colorado Springs, Colorado, United States

Torrance Memorial Physician Network - TRIO

🇺🇸

Torrance, California, United States

SCL Health Good Samaritan Medical Center Cancer Centers of Colorado

🇺🇸

Broomfield, Colorado, United States

Baptist MD Anderson Cancer Center

🇺🇸

Jacksonville, Florida, United States

Florida Cancer Specialists - South Region

🇺🇸

Fort Myers, Florida, United States

Poudre Valley Health System (PVHS)

🇺🇸

Fort Collins, Colorado, United States

Lombardi Cancer Center / Georgetown University Medical Center

🇺🇸

Washington, District of Columbia, United States

Florida Cancer Specialists - North Region

🇺🇸

Saint Petersburg, Florida, United States

Florida Cancer Specialists - East West Palm Beach, FL (SCRI)

🇺🇸

West Palm Beach, Florida, United States

Illinois Cancer Specialists - Arlington Heights

🇺🇸

Arlington Heights, Illinois, United States

Northside Hospital

🇺🇸

Canton, Georgia, United States

University of Maryland

🇺🇸

Baltimore, Maryland, United States

Ft Wayne Medical Oncology and Hematology, Inc TRIO

🇺🇸

Fort Wayne, Indiana, United States

Illinois Cancer Care

🇺🇸

Peoria, Illinois, United States

Maryland Oncology Hematology, P.A.

🇺🇸

Rockville, Maryland, United States

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

North Mississippi Medical Center Hematology Oncology - Tupelo

🇺🇸

Tupelo, Mississippi, United States

St. Vincent Frontier Cancer Center

🇺🇸

Billings, Montana, United States

Washington University in St Louis

🇺🇸

Saint Louis, Missouri, United States

Summit Medical Group

🇺🇸

Florham Park, New Jersey, United States

Rutgers Cancer Institute of New Jersey

🇺🇸

New Brunswick, New Jersey, United States

Saint Barnabas Medical Center Cancer Center

🇺🇸

Livingston, New Jersey, United States

Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

New York Oncology Hematology, P.C.

🇺🇸

Albany, New York, United States

Stony Brook University Cancer Center

🇺🇸

Stony Brook, New York, United States

Northwest Cancer Specialists, P.C.

🇺🇸

Tigard, Oregon, United States

University of Pennsylvania / Perelman Center for Advanced Medicine

🇺🇸

Philadelphia, Pennsylvania, United States

Brig Center for Cancer Care and Survivorship

🇺🇸

Knoxville, Tennessee, United States

Texas Oncology - Amarillo

🇺🇸

Amarillo, Texas, United States

Texas Oncology - DFW

🇺🇸

Dallas, Texas, United States

Mater Hospital

🇦🇺

Sydney, Other, Australia

Virginia Cancer Specialists, PC

🇺🇸

Fairfax, Virginia, United States

Peninsula Cancer Institute

🇺🇸

Newport News, Virginia, United States

Oncology & Hematology Associates of Southwest Virginia Inc dba Blue Ridge Cancer Care

🇺🇸

Salem, Virginia, United States

Saint Francis Hospital / Bon Secours - Virginia

🇺🇸

Midlothian, Virginia, United States

Swedish Cancer Institute - Edmonds

🇺🇸

Edmonds, Washington, United States

Swedish Cancer Institute - Issaquah

🇺🇸

Issaquah, Washington, United States

Peter MacCallum Cancer Centre

🇦🇺

Melbourne, Other, Australia

Austin Health

🇦🇺

Melbourne, Other, Australia

Westmead Hospital

🇦🇺

Westmead, Other, Australia

Breast Cancer Research Centre

🇦🇺

Nedlands, Other, Australia

LKH- Universitat Klinikum Graz

🇦🇹

Graz, Other, Austria

Medizinische Universitat Innsbruck

🇦🇹

Innsbruck, Other, Austria

LKH Salzburg, Universitatsklinikum der PMU

🇦🇹

Salzburg, Other, Austria

Medizinische Universitat Wien

🇦🇹

Vienna, Other, Austria

Klinik Ottakring

🇦🇹

Vienna, Other, Austria

Institut Jules Bordet

🇧🇪

Anderlecht, Other, Belgium

Cliniques Universitaires Saint Luc

🇧🇪

Brussels, Other, Belgium

Grand Hôpital de Charleroi - Saint-Joseph

🇧🇪

Charleroi, Other, Belgium

Universitair Ziekenhuis Antwerpen

🇧🇪

Edegem, Other, Belgium

Academisch Ziekenhuis Groeninge

🇧🇪

Kortrijk, Other, Belgium

University of Alberta / Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

CHU de Liege

🇧🇪

Liege, Other, Belgium

CHU UCL Namur-Site de Saint Elisabeth

🇧🇪

Namur, Other, Belgium

Universitair Ziekenhuis Leuven

🇧🇪

Leuven, Other, Belgium

Cancer Centre of Southeastern Ontario At Kingston General Hospital

🇨🇦

Kingston, Ontario, Canada

University Health Network, Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

London Health Sciences Centre - Victoria Hospital

🇨🇦

London, Ontario, Canada

University of Ottawa / Ottawa General Hospital

🇨🇦

Ottawa, Ontario, Canada

Centre Hospitalier de l'Universite de Montreal

🇨🇦

Montreal, Quebec, Canada

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

Saskatoon Cancer Centre

🇨🇦

Saskatoon, Saskatchewan, Canada

Hopital du Saint-Sacrement, CHU de Quebec-Universite Laval

🇨🇦

Quebec, Canada

Cancer Hospital Chinese Academy of Medical Sciences

🇨🇳

Beijing City, Other, China

Peking University People's Hospital

🇨🇳

Beijing, Other, China

Jilin Province Cancer Hospital

🇨🇳

Changghun, Other, China

Hunan Cancer Hospital

🇨🇳

Changsha, Other, China

Sun Yat-sen University Cancer Center

🇨🇳

Guangzhou City, Other, China

Guangdong Provincial People's Hospital

🇨🇳

Guangzhou, Other, China

Zhejiang Cancer Hospital

🇨🇳

Hangzhou City, Other, China

First Affiliated Hospital of Zhejiang University

🇨🇳

Hangzhou City, Other, China

The Second Affiliated Hospital of Zhejiang University School of Medicine

🇨🇳

Hangzhou, Other, China

Shandong Cancer Hospital

🇨🇳

Jinan, Other, China

Shengjing Hospital of China Medical University

🇨🇳

Shenyang City, Other, China

Gulou Hospital Affiliated to Nanjing University Medical College

🇨🇳

Nanjing, Other, China

Tianjin Medical University - Cancer Institute & Hospital

🇨🇳

Tianjin, Other, China

Hubei Cancer Hospital

🇨🇳

Wuhan, Other, China

The Affiliated Hospital of Xuzhou Medical College

🇨🇳

Xuzhou, Other, China

The Affiliated Hospital of Guangdong Medical University

🇨🇳

Zhan Jiang City, Other, China

Henan Cancer Hospital

🇨🇳

Zhengzhou, Other, China

Zigong First People's Hospital

🇨🇳

Zigong City, Other, China

Bejing Hospital

🇨🇳

Bejing, China

Wuhan University

🇨🇳

Wuhan, Other, China

The First Affiliated Hospital of Xi'an Jiaotong University

🇨🇳

Xi'an, Other, China

Xi'An International Medical Center Hospital

🇨🇳

Xi'An, Other, China

Xuzhou Central Hospital

🇨🇳

Xuzhou, Other, China

Center of Women and Children Hospital of Guangdong Province

🇨🇳

Guangzhou, China

Nanchang Third Hospital

🇨🇳

Nanchang City, China

Guangxi Medical University Affiliated Tumor Hospital

🇨🇳

Nanning, China

Rigs Hospiltalet

🇩🇰

Copenhagen, Other, Denmark

Aalborg Universitetshospital

🇩🇰

Aalborg, Other, Denmark

Aarhus University Hospital

🇩🇰

Aarhus N, Other, Denmark

Herlev Hospital

🇩🇰

Herlev, Other, Denmark

Odense University Hospital

🇩🇰

Odense C, Other, Denmark

Sygehus Lillebaelt - Vejle Sygehus

🇩🇰

Vejle, Other, Denmark

University Hospital of Besancon

🇫🇷

Besancon cedex, Other, France

Hospital Center Regional University Morvan De Brest

🇫🇷

Brest, Other, France

Centre de Lutte contre le Cancer - Francois Baclesse

🇫🇷

Caen Cedex 5, Other, France

Hopital Europeen Georges Pompidou

🇫🇷

Cedex 15, Other, France

Center Georges Francois Leclerc

🇫🇷

Dijon, Other, France

Clinique Victor Hugo Le Mans

🇫🇷

Le Mans, Other, France

Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes

🇫🇷

Lyon cedex 08, Other, France

Institute Curie - Centre de Lutte Contre Le Cancer CLCC de Paris

🇫🇷

Paris, Other, France

Institut Paoli Calmettes

🇫🇷

Marseille, Other, France

Centre Henri Becquerel / Centre Regional de Lutte Contre le Cancer

🇫🇷

Rouen, Other, France

Hopital Saint-Louis / Service d'Hematologie

🇫🇷

Paris Cedex 10, Other, France

Hopitaux Universitaires de Strasbourg

🇫🇷

Strasbourg, Other, France

Institut Claudius Regaud IUCT-O

🇫🇷

Toulouse Cedex 9, Other, France

CHU Tours - Hopital Bretonneau

🇫🇷

TOURS Cedex 09, Other, France

Helios Klinikum Berlin-Buch

🇩🇪

Berlin, Other, Germany

Stadtisches Klinikum Dessau

🇩🇪

Dessau-Rosslau, Other, Germany

Kliniken Essen-Mitte - Evang. Huyssens-Stiftung

🇩🇪

Essen, Other, Germany

CHOP GmbH

🇩🇪

Frankfurt, Other, Germany

Universitatsklinikum Heidelberg

🇩🇪

Heidelberg, Other, Germany

Universitatsklinikum Schleswig-Holstein

🇩🇪

Kiel, Other, Germany

Universitaetsklinikum Hamburg-Eppendorf (UKE)

🇩🇪

Hamburg, Other, Germany

InVO- Institut fUr Versorgungsforschung in der onkologie GbR

🇩🇪

Koblenz, Other, Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

🇩🇪

Mainz, Other, Germany

Klinikum Rechts der Isar der Technischen Universitaet Muenchen

🇩🇪

Muenchen, Other, Germany

Sana Klinikum Offenbach GmbH

🇩🇪

Offenbach am Main, Other, Germany

University of Rostock

🇩🇪

Rostock, Other, Germany

Klinikum der Universitat Munchen

🇩🇪

Munchen, Other, Germany

Shaare Zedek Medical Center

🇮🇱

Jerusalem, Other, Israel

Meir Medical Center

🇮🇱

Kfar Saba, Other, Israel

Rabin Medical Center

🇮🇱

Petach Tikva, Other, Israel

Kaplan Medical Center

🇮🇱

Rehovot, Other, Israel

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

🇮🇹

Bologna, Other, Italy

Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo FPO - IRCCS

🇮🇹

Candiolo, Other, Italy

Irccs Irst

🇮🇹

Meldola, Other, Italy

Istituto Europeo di Oncologia

🇮🇹

Milano, Other, Italy

Seconda Università degli Studi di Napoli, AOU

🇮🇹

Napoli, Other, Italy

Nuovo Ospedale di Prato - Santo Stefano

🇮🇹

Prato, Other, Italy

Ospedale degli Infermi

🇮🇹

Rimini, Other, Italy

Policlinico Universitario Agostino Gemelli

🇮🇹

Roma, Other, Italy

Azienda Ospedaliera S. Maria di Terni

🇮🇹

Terni, Other, Italy

A.O.U. - Ospedali Riuniti di Ancona

🇮🇹

Torrette, Other, Italy

Chiba Cancer Center

🇯🇵

Chiba, Other, Japan

National Cancer Center Hospital

🇯🇵

Chuo-ku, Other, Japan

National Hospital Organization Kyushu Cancer Center

🇯🇵

Fukuoka-shi, Other, Japan

Hiroshima City Hiroshima Citizens Hospital

🇯🇵

Hiroshima, Other, Japan

University of Tsukuba Hospital

🇯🇵

Ibaraki, Other, Japan

National Cancer Center Hospital East

🇯🇵

Kashiwa-shi, Other, Japan

Saitama Cancer Center

🇯🇵

Kitaadachi-gun, Other, Japan

Kumamoto Shinto General Hospital

🇯🇵

Kumamoto, Other, Japan

NHO Shikoku Cancer Center

🇯🇵

Matsuyama, Other, Japan

Aichi Cancer Center

🇯🇵

Nagoya-shi, Other, Japan

Hakuaikai Sagara Hospital/Breast Surgery

🇯🇵

Kagosima, Other, Japan

Kameda General Hospital

🇯🇵

Kamogawa, Other, Japan

Hyogo College of Medicine Hospital

🇯🇵

Nishinomiya, Other, Japan

National Hospital Organization Osaka

🇯🇵

Osaka, Other, Japan

Osaka International Cancer Institute

🇯🇵

Osaka, Other, Japan

National Hospital Organization Hokkaido Cancer Center

🇯🇵

Sapporo, Other, Japan

Shizuoka Cancer Center

🇯🇵

Sunto-Gun, Other, Japan

The Cancer Institute Hospital of JFCR

🇯🇵

Tokyo, Other, Japan

Kanagawa Cancer Center

🇯🇵

Yokohama, Other, Japan

National Cancer Center

🇰🇷

Goyang-si, Other, Korea, Republic of

Seoul National University Bundang Hospital

🇰🇷

Seongnam-si, Other, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Other, Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Other, Korea, Republic of

Korea University Anam Hospital

🇰🇷

Seoul, Other, Korea, Republic of

Asan Medical Center - Oncology

🇰🇷

Seoul, Other, Korea, Republic of

Isala Ziekenhuis Zwolle

🇳🇱

AB Zwolle, Other, Netherlands

Netherlands Cancer Institute

🇳🇱

Amsterdam, Other, Netherlands

Samsung Medical Center

🇰🇷

Seoul, Other, Korea, Republic of

Reinier de Graaf Hospital

🇳🇱

Delft, Other, Netherlands

University Medical Center Groningen

🇳🇱

Groningen, Other, Netherlands

Martini Ziekenhuis

🇳🇱

Groningen, Other, Netherlands

Maastricht University Medical Center

🇳🇱

Maastricht, Other, Netherlands

Erasmus Medisch Centrum Daniel Den Hoed

🇳🇱

Rotterdam, Other, Netherlands

National University Cancer Institute, Singapore

🇸🇬

Singapore, Other, Singapore

Amphia Ziekenhuis

🇳🇱

Breda, Other, Netherlands

National Cancer Centre Singapore

🇸🇬

Singapore, Other, Singapore

Hospital del Mar

🇪🇸

Barcelona, Other, Spain

Hospital General Universitario Gregorio Marañon

🇪🇸

Madrid, Other, Spain

Hospital Ruber Internacional

🇪🇸

Madrid, Other, Spain

Hospital Clinico San Carlos

🇪🇸

Madrid, Other, Spain

Hospital Universitario HM Sanchinarro

🇪🇸

Madrid, Other, Spain

Hospital Universitario Virgen de la Victoria

🇪🇸

Malaga, Other, Spain

Hospital Universitario Son Espases

🇪🇸

Palma de Mallorca, Other, Spain

L'Institut Catala d'Oncologia

🇪🇸

Saint Joan Despi, Other, Spain

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Other, Spain

Hospital Universitario Reina Sofia

🇪🇸

Cordoba, Other, Spain

Hospital Universitario de Canarias

🇪🇸

San Cristóbal de la Laguna, Other, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Other, Spain

Hospital Clinico Universitario de Valencia

🇪🇸

Valencia, Other, Spain

Hospital Universitario Miguel Servet

🇪🇸

Zaragoza, Other, Spain

Goteborgs Universitet - Sahlgrenska Akademin - Institutionen For Kliniska Vetenskaper (Institute Of Clinical Sciences)

🇸🇪

Gothenburg, Other, Sweden

Skanes University Hospital - Universitetssjukhus

🇸🇪

Lund, Other, Sweden

Orebro University Hospital

🇸🇪

Orebro, Other, Sweden

Ryhov Hospital

🇸🇪

Jonkoping, Other, Sweden

Onkologklinike Sodersjukhuset

🇸🇪

Stockholm, Other, Sweden

University Hospital Basel - Brustzentrum

🇨🇭

Basel, Other, Switzerland

Institute of Oncology of Southern Switzerland

🇨🇭

Bellinzona, Other, Switzerland

University Hospital Lausanne CHUV

🇨🇭

Lausanne, Other, Switzerland

Kantonsspital Winterthur (KSW)

🇨🇭

Winterthur, Other, Switzerland

National Cheng-Kung University Hospital

🇨🇳

Tainan, Other, Taiwan

National Taiwan University Hospital

🇨🇳

Tainan, Other, Taiwan

University Hospitals Birmingham NHS Foundation Trust

🇬🇧

Birmingham, Other, United Kingdom

The University of Edinburgh

🇬🇧

Edinburgh, Other, United Kingdom

Addenbrooke's Hospital

🇬🇧

Cambridge, Other, United Kingdom

Oxford University Hospitals

🇬🇧

Headington, Other, United Kingdom

The Royal Marsden NHS Foundation Trust (RM)

🇬🇧

London, Other, United Kingdom

Sarah Cannon Research Institute UK

🇬🇧

London, Other, United Kingdom

Maidstone and Tunbridge Wells NHS Trust

🇬🇧

Maidstone, Other, United Kingdom

The Christie NHS Foundation Trust

🇬🇧

Manchester, Other, United Kingdom

The Newcastle upon Tyne Hospitals NHS Foundation Trust

🇬🇧

Newcastle Upon Tyne, Other, United Kingdom

Mount Vernon Hospital, UK

🇬🇧

Northwood, Other, United Kingdom

The Royal Marsden Hospital (Surrey)

🇬🇧

Sutton, Other, United Kingdom

AdventHealth Cancer Institute

🇺🇸

Orlando, Florida, United States

Orlando Health, Inc. TRIO

🇺🇸

Orlando, Florida, United States

University of Michigan Comprehensive Cancer Center

🇺🇸

Ann Arbor, Michigan, United States

University of Miami

🇺🇸

Miami, Florida, United States

The Center for Cancer and Blood Disorders: Fortworth

🇺🇸

Fort Worth, Texas, United States

Helen F. Graham Cancer Center / Christiana Care Health Systems

🇺🇸

Newark, Delaware, United States

UCLA Department of Medicine - Hematology & Oncology

🇺🇸

Santa Monica, California, United States

Augusta University

🇺🇸

Augusta, Georgia, United States

University of South Alabama - Mitchell Cancer Institute

🇺🇸

Mobile, Alabama, United States

Saint Luke's Cancer Institute LLC

🇺🇸

Kansas City, Missouri, United States

HCA Midwest Health Kansas City

🇺🇸

Kansas City, Missouri, United States

UNC Lineberger Comprehensive Cancer Center / University of North Carolina

🇺🇸

Chapel Hill, North Carolina, United States

Ochsner Medical Center

🇺🇸

New Orleans, Louisiana, United States

Texas Oncology - Austin Central

🇺🇸

Austin, Texas, United States

Kapi'olani Medical Center for Women and Children

🇺🇸

Honolulu, Hawaii, United States

Kaiser Permanente Moanalua Medical Center

🇺🇸

Honolulu, Hawaii, United States

CHI Saint Joseph Medical Group Cancer Care Center

🇺🇸

Lexington, Kentucky, United States

Royal Cornwall Hospitals NHS Trust

🇬🇧

Truro, Other, United Kingdom

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

Queen Elizabeth II Health Sciences Centre

🇨🇦

Halifax, Nova Scotia, Canada

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