A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer
HER2-positive Breast Cancer
About this trial
This is an interventional treatment trial for HER2-positive Breast Cancer focused on measuring Seattle Genetics
Eligibility Criteria
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), subjects 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
- 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
Subjects 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
- 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), subjects must not have any of the following:
- Any untreated brain lesions >2 cm in size
- Ongoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent).
- Any brain lesion thought to require immediate local therapy
- Known or concurrent leptomeningeal disease as documented by the investigator
- Poorly controlled generalized or complex partial seizures
Sites / Locations
- University of South Alabama - Mitchell Cancer Institute
- Ironwood Cancer & Research Centers - Chandler
- Banner MD Anderson Cancer Center
- Cancer Treatment Centers of America / Western Regional Medical Center
- Arizona Oncology Associates, PC - HAL
- Arizona Oncology Associates, PC - HOPE
- St. Bernards Medical Center
- City of Hope National Medical Center
- California Cancer Associates for Research and Excellence Inc (cCARE)
- St. Joseph Heritage Healthcare TRIO
- Chao Family Comprehensive Cancer Center University of California Irvine
- University of California Irvine - Newport
- University of California Davis
- San Francisco General Hospital
- University of California at San Francisco
- UCLA Department of Medicine - Hematology & Oncology
- Torrance Memorial Physician Network - TRIO
- Kaiser Permanente Medical Center Northern California
- Rocky Mountain Cancer Centers - Aurora
- University of Colorado Hospital / University of Colorado
- SCL Health Good Samaritan Medical Center Cancer Centers of Colorado
- University of Colorado Health Memorial Hospital
- Cancer Centers of Colorado - Denver
- Poudre Valley Health System (PVHS)
- Helen F. Graham Cancer Center / Christiana Care Health Systems
- Lombardi Cancer Center / Georgetown University Medical Center
- Florida Cancer Specialists - South Region
- Baptist MD Anderson Cancer Center
- University of Miami
- Miami Cancer Institute at Baptist Health, Inc.
- AdventHealth Cancer Institute
- Orlando Health, Inc. TRIO
- Florida Cancer Specialists - North Region
- H. Lee Moffitt Cancer Center and Research Institute
- Florida Cancer Specialists - East West Palm Beach, FL (SCRI)
- Winship Cancer Institute / Emory University School of Medicine
- Northside Hospital
- Augusta University
- Kaiser Permanente Moanalua Medical Center
- Kapi'olani Medical Center for Women and Children
- Illinois Cancer Specialists - Arlington Heights
- Rush University Medical Center
- University of Chicago Medical Center
- Illinois Cancer Care
- Ft Wayne Medical Oncology and Hematology, Inc TRIO
- University of Kansas Medical Center
- CHI Saint Joseph Medical Group Cancer Care Center
- Ochsner Medical Center
- University of Maryland
- Mercy Medical Center -Weinberg Center
- American Oncology Networks LLC
- Maryland Oncology Hematology, P.A.
- Beth Israel Deaconess Medical Center
- Dana Farber Cancer Institute
- University of Michigan Comprehensive Cancer Center
- Henry Ford Health System
- Minnesota Oncology Hematology P.A.
- North Mississippi Medical Center Hematology Oncology - Tupelo
- Saint Luke's Cancer Institute LLC
- HCA Midwest Health Kansas City
- Washington University in St Louis
- St. Vincent Frontier Cancer Center
- Nebraska Cancer Specialists
- Comprehensive Cancer Centers of Nevada
- Summit Medical Group
- Saint Barnabas Medical Center Cancer Center
- Rutgers Cancer Institute of New Jersey
- New York Oncology Hematology, P.C.
- Stony Brook University Cancer Center
- UNC Lineberger Comprehensive Cancer Center / University of North Carolina
- Levine Cancer Institute
- Duke University Medical Center
- Providence Portland Medical Center
- Oregon Health and Science University
- Northwest Cancer Specialists, P.C.
- University of Pennsylvania / Perelman Center for Advanced Medicine
- Cancer Treatment Centers of America / Eastern Regional Medical Center
- Brig Center for Cancer Care and Survivorship
- Tennessee Oncology-Nashville/Sarah Cannon Research Institute
- Texas Oncology - Amarillo
- Texas Oncology - Austin Central
- Texas Oncology - DFWW
- Texas Oncology - Methodist Dallas Cancer Center
- Texas Oncology - Medical City Dallas
- Texas Oncology - Baylor Sammons Cancer Center
- University of Texas Southwestern Medical Center
- The Center for Cancer and Blood Disorders: Fortworth
- Texas Oncology - Houston Memorial City
- MD Anderson Cancer Center / University of Texas
- Baylor Clinic
- Oncology Consultants, PA
- Texas Oncology - San Antonio Medical Center
- Huntsman Cancer Institute/University of Utah
- Virginia Cancer Specialists, PC
- Saint Francis Hospital / Bon Secours - Virginia
- Peninsula Cancer Institute
- Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
- Swedish Cancer Institute - Edmonds
- Swedish Cancer Institute - Issaquah
- Swedish Cancer Institute
- Peter MacCallum Cancer Centre
- Austin Health
- Breast Cancer Research Centre
- Mater Hospital
- Westmead Hospital
- LKH- Universitat Klinikum Graz
- Medizinische Universitat Innsbruck
- LKH Salzburg, Universitatsklinikum der PMU
- Medizinische Universitat Wien
- Klinik Ottakring
- Institut Jules Bordet
- Cliniques Universitaires Saint Luc
- Grand Hôpital de Charleroi - Saint-Joseph
- Universitair Ziekenhuis Antwerpen
- Academisch Ziekenhuis Groeninge
- CHU de Liege
- Universitair Ziekenhuis Leuven
- CHU UCL Namur-Site de Saint Elisabeth
- University of Alberta / Cross Cancer Institute
- Queen Elizabeth II Health Sciences Centre
- Cancer Centre of Southeastern Ontario At Kingston General Hospital
- London Health Sciences Centre - Victoria Hospital
- University of Ottawa / Ottawa General Hospital
- University Health Network, Princess Margaret Hospital
- Centre Hospitalier de l'Universite de Montreal
- Jewish General Hospital
- Saskatoon Cancer Centre
- Hopital du Saint-Sacrement, CHU de Quebec-Universite Laval
- Cancer Hospital Chinese Academy of Medical SciencesRecruiting
- Jilin Province Cancer HospitalRecruiting
- Hunan Cancer HospitalRecruiting
- Sun Yat-sen University Cancer CenterRecruiting
- Zhejiang Cancer HospitalRecruiting
- First Affiliated Hospital of Zhejiang UniversityRecruiting
- The Second Affiliated Hospital of Zhejiang University School of MedicineRecruiting
- Gulou Hospital Affiliated to Nanjing University Medical CollegeRecruiting
- Shengjing Hospital of China Medical UniversityRecruiting
- Tianjin Medical University - Cancer Institute & HospitalRecruiting
- Hubei Cancer HospitalRecruiting
- Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and TechnologyRecruiting
- Wuhan UniversityRecruiting
- The First Affiliated Hospital of Xi'an Jiaotong UniversityRecruiting
- Xi'An International Medical Center HospitalRecruiting
- Xuzhou Central HospitalRecruiting
- The Affiliated Hospital of Guangdong Medical UniversityRecruiting
- Henan Cancer HospitalRecruiting
- Bejing HospitalRecruiting
- Center of Women and Children Hospital of Guangdong ProvinceRecruiting
- Nanchang Third HospitalRecruiting
- Guangxi Medical University Affiliated Tumor HospitalRecruiting
- Aalborg Universitetshospital
- Aarhus University Hospital
- Rigs Hospiltalet
- Herlev Hospital
- Odense University Hospital
- Sygehus Lillebaelt - Vejle Sygehus
- University Hospital of Besancon
- Hospital Center Regional University Morvan De Brest
- Centre de Lutte contre le Cancer - François Baclesse
- Hopital Europeen Georges Pompidou
- Center Georges Francois Leclerc
- Clinique Victor Hugo Le Mans
- Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes
- Institut Paoli Calmettes
- Hopital Saint-Louis / Service d'Hematologie
- Institute Curie - Centre de Lutte Contre Le Cancer CLCC de Paris
- Centre Henri Becquerel / Centre Regional de Lutte Contre le Cancer
- Hopitaux Universitaires de Strasbourg
- Institut Claudius Regaud IUCT-O
- CHU Tours - Hopital Bretonneau
- Helios Klinikum Berlin-Buch
- Stadtisches Klinikum Dessau
- Kliniken Essen-Mitte - Evang. Huyssens-Stiftung
- CHOP GmbH
- Universitaetsklinikum Hamburg-Eppendorf (UKE)
- Universitatsklinikum Heidelberg
- Universitatsklinikum Schleswig-Holstein
- InVO- Institut fUr Versorgungsforschung in der onkologie GbR
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
- Klinikum Rechts der Isar der Technischen Universitaet Muenchen
- Klinikum der Universitat Munchen
- Sana Klinikum Offenbach GmbH
- University of Rostock
- Shaare Zedek Medical Center
- Meir Medical Center
- Rabin Medical Center
- Kaplan Medical Center
- Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
- Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo FPO - IRCCS
- Irccs Irst
- Istituto Europeo di Oncologia
- Seconda Università degli Studi di Napoli, AOU
- Nuovo Ospedale di Prato - Santo Stefano
- Ospedale degli Infermi
- Policlinico Universitario Agostino Gemelli
- Azienda Ospedaliera S. Maria di Terni
- A.O.U. - Ospedali Riuniti di Ancona
- Chiba Cancer Center
- National Cancer Center Hospital
- National Hospital Organization Kyushu Cancer Center
- Hiroshima City Hiroshima Citizens Hospital
- University of Tsukuba Hospital
- Hakuaikai Sagara Hospital/Breast Surgery
- Kameda General Hospital
- National Cancer Center Hospital East
- Saitama Cancer Center
- Kumamoto Shinto General Hospital
- NHO Shikoku Cancer Center
- Aichi Cancer Center
- Hyogo College of Medicine Hospital
- National Hospital Organization Osaka
- Osaka International Cancer Institute
- National Hospital Organization Hokkaido Cancer Center
- Shizuoka Cancer Center
- The Cancer Institute Hospital of JFCR
- Kanagawa Cancer Center
- National Cancer Center
- Seoul National University Bundang Hospital
- Korea University Anam Hospital
- Seoul National University Hospital
- Severance Hospital, Yonsei University Health System
- Asan Medical Center - Oncology
- Samsung Medical Center
- Isala Ziekenhuis Zwolle
- Netherlands Cancer Institute
- Amphia Ziekenhuis
- Reinier de Graaf Hospital
- University Medical Center Groningen
- Martini Ziekenhuis
- Maastricht University Medical Center
- Erasmus Medisch Centrum Daniel Den Hoed
- National University Cancer Institute, Singapore
- National Cancer Centre Singapore
- Hospital del Mar
- Hospital Universitari Vall d'Hebron
- Hospital Universitario Reina Sofia
- Hospital General Universitario Gregorio Marañon
- Hospital Ruber Internacional
- Hospital Clinico San Carlos
- Hospital Universitario HM Sanchinarro
- Hospital Universitario Virgen de la Victoria
- Hospital Universitario Son Espases
- L'Institut Catala d'Oncologia
- Hospital Universitario de Canarias
- Hospital Universitario Virgen del Rocio
- Hospital Clinico Universitario de Valencia
- Hospital Universitario Miguel Servet
- Goteborgs Universitet - Sahlgrenska Akademin - Institutionen For Kliniska Vetenskaper (Institute Of Clinical Sciences)
- Ryhov Hospital
- Skanes University Hospital - Universitetssjukhus
- Orebro University Hospital
- Onkologklinike Sodersjukhuset
- University Hospital Basel - Brustzentrum
- Institute of Oncology of Southern Switzerland
- University Hospital Lausanne CHUV
- Kantonsspital Winterthur (KSW)
- National Cheng-Kung University Hospital
- National Taiwan University Hospital
- University Hospitals Birmingham NHS Foundation Trust
- Addenbrooke's Hospital
- The University of Edinburgh
- Oxford University Hospitals
- The Royal Marsden NHS Foundation Trust (RM)
- Sarah Cannon Research Institute UK
- Maidstone and Tunbridge Wells NHS Trust
- The Christie NHS Foundation Trust
- The Newcastle upon Tyne Hospitals NHS Foundation Trust
- Mount Vernon Hospital, UK
- The Royal Marsden Hospital (Surrey)
- Royal Cornwall Hospitals NHS Trust
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Tucatinib + T-DM1
Placebo + T-DM1
Tucatinib + T-DM1
Placebo + T-DM1