A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer
Phase 3 – large-scale trial before approval
Conditions:
HER2 Positive Breast Cancer
Sponsor: Seagen, a wholly owned subsidiary of Pfizer
trial.available_in:
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Overview
This study is being done to see if tucatinib works better than placebo when given with other drugs to treat participants with HER2-positive breast cancer. A placebo is a pill that looks the same as tucatinib but has no medicine in it. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.
Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic).
In this study, all participants will get either tucatinib or placebo. Participants will be assigned randomly to a group. This is a blinded study, so patients and their doctors will not know which group a participant is in.
All participants will also get trastuzumab and pertuzumab. These are 2 drugs used to treat this type of cancer.
Description
Control arm: Placebo given orally twice daily plus trastuzumab and pertuzumab every 21 days
Experimental arm: Tucatinib 300 mg given orally twice daily plus trastuzumab and pertuzumab every 21 days
Trastuzumab and pertuzumab will be administered as follows:
• Trastuzumab will be given intravenously (IV) at a dose of 6 mg/kg or subcutaneously (SC) at a fixed dose of 600 mg, once every 21 days.
AND
* Pertuzumab will be given IV at 420 mg every 21 days. OR
* Fixed dose combination of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given SC, once every 21 days, in lieu of trastuzumab and pertuzumab individually.
Who can participate
Inclusion Criteria:
* Centrally confirmed HER2+ breast carcinoma according to the 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines prior to randomization (defined as a 3+ score on immunohistochemistry (IHC) and/or 2+ IHC and concurrent positive by ISH).
* Have unresectable locally advanced or metastatic disease.
* If recurrent (after \[neo\]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab and pertuzumab received in the early breast cancer setting for advanced HER2+ disease.
* Have received 4-8 cycles of pre-study induction therapy including only trastuzumab, pertuzumab, and taxane as first-line of therapy for the treatment of advanced breast cancer prior to study enrollment. Participants are eligible provided they are without evidence of disease progression following completion of induction therapy.
* Known hormone receptor status (per local guidelines; may be hormone receptor positive \[HR+\] or negative \[HR-\])
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* CNS Inclusion - Based on screening contrast-enhanced brain magnetic resonance imaging (MRI), participants may have any of the following:
* No evidence of brain metastases
* Untreated brain metastases which are asymptomatic not needing immediate local treatment and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane
* Previously treated brain metastases which are asymptomatic
* Brain metastases previously treated with local therapy must not have progressed since treatment
Exclusion Criteria:
* Prior treatment with any tyrosine kinase inhibitor targeting HER2 and/or epidermal growth factor receptor (EGFR) including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and ≥ 12 months have elapsed since last neratinib dose prior to start of study drug)
* Unable to undergo contrast-enhanced MRI of the brain
* CNS Exclusion - Based on screening brain MRI and clinical assessment
* Symptomatic brain metastasis after CNS-directed local therapy
* Progression of brain metastases since starting first line trastuzumab, pertuzumab, and taxane
* Ongoing use of systemic corticosteroids at a total daily dose of \>2 mg of dexamethasone (or equivalent)
* Any untreated brain lesion in an anatomic site which may pose risk to participant
* Known or suspected leptomeningeal disease (LMD)
* Poorly controlled (\>1/week) seizures, or other persistent neurologic symptoms
Interventions
Tucatinib
DRUG
Trastuzumab
DRUG
Pertuzumab
DRUG
Combination product: Trastuzumab + Pertuzumab
DRUG
Placebo
DRUG
Locations
307
Australia (9)
Cancer Research SA
Adelaide , South Australia
St Andrews Medical Centre
Adelaide , South Australia
Flinders Medical Centre
Bedford Park , South Australia
Box Hill Hospital
Box Hill , Victoria
Chris O'Brien Lifehouse
Camperdown , New South Wales
Austin Health
Heidelberg , Victoria
Macquarie University Clinical Trials Unit.
Macquarie University , New South Wales
St John of God Subiaco Hospital Clinical Trials Unit Bendat Family Comprehensive Cancer Centre
Subiaco , Washington
Western Sydney Local Health District (WSLHD), Westmead Hospital
Westmead , New South Wales
Austria (5)
Medizinische Universität Graz
Graz
Medizinische Universitat Graz
Graz
Ordensklinikum Linz GmbH Barmherzige Schwestern
Linz
Ordination Priv.-Doz. Dr. Michael Hubalek
Schwaz , Other
Medizinische Universitat Wien Universitatsklinik Fur Frauenheilkunde
Vienna
Belgium (4)
Jules Bordet lnstituut
Anderlecht
Universitair Ziekenhuis Brussel (UZ Brussel)
Brussels
Cliniques Universitaires Saint-Luc
Brussels
Clinique St-Pierre
Ottignies
Brazil (17)
Fundacao Pio XII, Hospital do Amor de Barretos
Barretos , São Paulo
CRIO - Centro Regional lntegrado de Oncologia
Fortaleza , Ceará
Hospital Araujo Jorge
Goiânia , Goiás
Fundacao Dr Amaral Carvalho
Jaú , São Paulo
Hospital Do Cancer De Londrina
Londrina , Paraná
Liga Norte-Rio Grandense Contra o Cancer
Natal , Rio Grande do Norte
Hospital de Clinicas de Porto Alegre
Porto Alegre , Rio Grande do Sul
Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa - Hospital do Cancer Mae de Deu
Porto Alegre , Rio Grande do Sul
Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa - Hospital do Cancer Mae de Deu
Porto Alegre , Rio Grande do Sul
Irmandade da Santa Casa de Misericordia de Porto Alegre centro Multidisciplinar de pesquisa clinica
Porto Alegre/RS
CEPHO- Centro de Estudos e Pesquisas de Hematologia e Oncologia
Santo André , São Paulo
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
Santo André , São Paulo
Faculdade Regional de Medicina de Sao Jose do Rio Preto
São José do Rio Preto
ICESP- Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira
São Paulo
Sao Camilo Oncologia
São Paulo
Clinica de Pesquisas e Centro de Estudos em Oncologia Ginecologica e Mamária Ltda.
São Paulo
A.C. Camargo Câncer Center
Sao Paulo/SP , Other
Canada (8)
Centre integre universitaire de sante et de services sociaux du Saguenay-Lac-Saint-Jean
Chicoutimi , Quebec
Cross Cancer Institute
Edmonton , Alberta
BC Cancer Agency
Kelowna , British Columbia
Centre Hospitalier de l'Universite de Motreal (CHUM)
Montreal , Quebec
Jewish General Hospital
Montreal , Quebec
The Ottawa Hospital Cancer Centre
Ottawa , Ontario
Sunnybrook Research Institute
Toronto , Ontario
Mount Sinai Hospital
Toronto , Ontario
Chile (5)
Centro de Investigacion Clínica Bradford Hill
Recoleta , Santiago Metropolitan
Clinica Universidad Catolica del Maule
Talca
Clinica Alemana Temuco
Temuco
James Lind Centro De Investigacion Del Cancer
Temuco
Oncocentro Apys
Viña del Mar , Valparaiso
China (29)
Affiliated Hospital of Hebei University
Baoding , Hebei
Beijing Hospital
Beijing
Beijing Hospital
Beijing
The First Hospital of Jilin University
Changchun , Jilin
The Second Xiangya Hospital of Central South University
Changsha , Hunan
Guangdong Provincial People's Hospital
Guangzhou , Guangdong
The first Affiliated Hospital of Hainan Medical University
Haikou , Hainan
Zhejiang Cancer Hospital
Hangzhou , Zhejiang
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou , Zhejiang
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou , Zhejiang
The Second Hospital of Anhui Medical University
Hefei , Anhui
Jinan Central Hospital
Jinan , Shandong
Linyi Cancer Hospital
Linyi , Shandong
Liuzhou People's Hospital
Liuchow , Guangxi
Meizhou People's Hospital
Meizhou , Guangdong
The Second Affiliated Hospital of Nanchang University
Nanchang , Jiangxi
Nanjing Medical University (NMU) - Jiangsu Province Hospital
Nanjing , Jiangsu
Guangxi Medical University Affiliated Tumor Hospital
Nanning , Guangxi
The People's Hospital of Guangxi Zhuang Autonomous Region
Nanning , Guangxi
Ruijin Hospital of Shanghai Jiaotong University School of Medicine
Shanghai , Other
Fudan University Shanghai Cancer Center
Shanghai
Liaoning Cancer Hospital & Insitute
Shenyang , Liaoning
The First Affiliated Hospital of China Medical University
Shenyang , Liaoning
Tianjin Cancer Hospital Binhai Campus
Tianjin
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
Wuhan , Hubei
Hubei Cancer Hospital
Wuhan , Hubei
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an , Shaanxi
Shaanxi Provincial People's Hospital
Xi'an , Shaanxi
Henan Cancer Hospital
Zhengzhou , Henan
Czech Republic (6)
Ustavni lekarna Masarykuv onkologicky ustav
Brno , Other
Masarykuv Onkologicky Ustav
Brno
Vseobecna fakultni nemocnice v Praze
Prague
Fakultni Thomayerova nemocnice Onkologicka klinika 1. LF UK a FTN
Praha 4 - Krc , Other
Fakultni nemocnice v Motole Onkologicka klinika 2. LF UK a FN Motol
Praha 5 - Motol
Nemocnicni lekarna Fakultni nemocnice v Motole
Praha 5 - Motol
Finland (2)
Tampere University Hospital, FONK/RSYO
Tampere
Tampere University Hospital
Tampere
France (25)
Institut Sainte-Catherine.
Avignon , Other
Sainte Catherine lnstitut du Cancer Avignon Provence
Avignon , Other
CHU Besancon
Besançon
Hopital Avicenne
Bobigny
Institut Bergonie
Bordeaux , Cedex
CENTRE FRANCOIS BACLESSE - Service lmagerie medicale
Caen
Centre Francois Baclesse
Caen
Centre de Lutte contre le Cancer - François Baclesse
Caen
Centre Jean Perrin
Clermont-Ferrand
Center Georges-Francois Leclerc
Dijon , Other
Centre Oscar Lambret
Lille
Center Leon Berard
Lyon
Institut Regional du Cancer de Montpellier Service lmagerie medicale
Montpellier
Institut Régional du Cancer de Montpellier
Montpellier
Centre de Cancérologie du Grand Montpellier
Montpellier , Languedoc-roussillon
Centre Antoine Lacassagne
Nice
Hospices Civils de Lyon
Pierre-Bénite
"CARIO - Centre Armoricain de Radiotherapie lmagerie medicate et d'Oncologie -Hopital Prive des
Plérin
Centre Eugene Marquis
Rennes
Centre Henri Becquerel
Rouen
Centre Henri Becquerel / Centre Regional de Lutte Contre le Cancer
Rouen , Brittany Region
Institut Curie - site St-Cloud
Saint-Cloud
Institut de Cancerologie de lOuest - Site Rene Gauducheau
Saint-Herblain , Loire-atlantique
Institut de Cancerologie de lOuest-Saint Herblain
Saint-Herblain , Loire-atlantique
Centre de Lutte contre le Cancer Paul Strauss - CPS
Strasbourg
Germany (11)
"Universitatsklinikum Augsburg Klinik fur Frauenheilkunde und Geburtshilfe"
Augsburg
Charite Universtitatsmedizin Berlin Klinik fur Gynakologie mit Brustzentrum
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