Clinical trial • Phase III • Oncology
Tucatinib for HER2-positive breast cancer | Locally advanced breast cancer | Metastatic breast cancer
Phase III trial of Tucatinib for HER2-positive breast cancer | Locally advanced breast cancer | Metastatic breast cancer.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- HER2-positive breast cancer | Locally advanced breast cancer | Metastatic breast cancer
- Trial Stage
- Phase III
- Drug Modality
- Small molecule | ADC
Key dates
- Initial CTIS Submission Date
- 17-06-2024
- First CTIS Authorization Date
- 18-07-2024
Trial design
Randomised, control arm: placebo given po bid; t-dm1 3.6 mg/kg iv every 21 days. experimental arm: tucatinib 300 mg po bid; t-dm1 3.6 mg/kg iv every 21 days. Phase III trial across 36 sites in Sweden, Belgium, Spain and others.
- Randomised
- Yes
- Comparator
- Control arm: Placebo given PO BID; T-DM1 3.6 mg/kg IV every 21 days. Experimental arm: Tucatinib 300 mg PO BID; T-DM1 3.6 mg/kg IV every 21 days.
- Target Sample Size
- 466
Eligibility
Recruits 466 Vulnerable population selected. Informed consent will be obtained using the provided Subject Information and Informed Consent Forms (L1_SIS and ICF) documents listed for each Member State. No detailed information on assent or specific consent-age handling is available in the provided record..
- Vulnerable Population
- Vulnerable population selected. Informed consent will be obtained using the provided Subject Information and Informed Consent Forms (L1_SIS and ICF) documents listed for each Member State. No detailed information on assent or specific consent-age handling is available in the provided record.
Inclusion criteria
- {"criterion_text":"- Histologically confirmed HER2+ breast carcinoma as determined by a sponsor-designated central laboratory\n- History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination\n- Have progression of unresectable locally advanced/metastatic breast cancer after last systemic therapy, or be intolerant of last systemic therapy\n- Measurable or non-measurable disease assessable by RECIST v1.1\n- ECOG performance status score of 0 or 1\n- 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.\tBrain 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.\tParticipants 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.\tRelevant records of any CNS treatment must be available to allow for classification of target and non-target lesions"}
Exclusion criteria
- {"criterion_text":"- 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).\n- CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must not have any of the following: 1.\tAny untreated brain lesions >2 cm in size 2.\tOngoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent). 3.\tAny brain lesion thought to require immediate local therapy 4.\tKnown or concurrent leptomeningeal disease as documented by the investigator 5.\tPoorly controlled generalized or complex partial seizures"}
Endpoints
Primary endpoints
- {"endpoint_text":"- PFS per RECIST v1.1, as determined by investigator assessment","definition_or_measurement_approach":"Determined by investigator assessment per RECIST v1.1"}
Secondary endpoints
- {"endpoint_text":"- OS\n- PFS.BM per RECIST v1.1, as determined by investigator assessment\n- ORR per RECIST v1.1, by investigator assessment\n- OS.BM","definition_or_measurement_approach":"OS: overall survival. PFS.BM and ORR: assessed by investigator per RECIST v1.1. OS.BM: overall survival in subjects with brain metastases at baseline."}
Recruitment
- Planned Sample Size
- 466
- Recruitment Window Months
- 74
- Consent Approach
- Informed consent obtained from subjects using country-specific Subject Information and Informed Consent Forms (L1_SIS and ICF) as listed in the documents (multiple country/language versions available: EN, FR, NL, IT, DE, DK, etc.). The record does not provide further details on assent or age-specific consent procedures.
Geography
- Total Number Of Sites
- 36
- Total Number Of Participants
- 101
Sweden
- Latest Decision Or Authorization Date
- 22-07-2024
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- Region Joenkoepings Laen
- Department Name
- Department of Oncology
- Principal Investigator Name
- Maria Ekholm
- Principal Investigator Email
- maria.ekholm@rjl.se
- Contact Person Name
- Maria Ekholm
- Contact Person Email
- maria.ekholm@rjl.se
- Site Name
- Sahlgrenska University Hospital-Vaestra Goetalandsregionen
- Department Name
- Institutionen For Kliniska Vetenskaper (Institute Of Clinical Sciences)
- Principal Investigator Name
- Barbro Linderholm
- Principal Investigator Email
- barbro.linderholm@oncology.gu.se
- Contact Person Name
- Barbro Linderholm
- Contact Person Email
- barbro.linderholm@oncology.gu.se
Belgium
- Latest Decision Or Authorization Date
- 22-07-2024
- Number Of Sites
- 6
- Number Of Participants
- 16
Sites
- Site Name
- Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
- Department Name
- Service d'oncologie
- Principal Investigator Name
- Donatienne Taylor
- Principal Investigator Email
- donatienne.taylor@uclouvain.be
- Contact Person Name
- Donatienne Taylor
- Contact Person Email
- donatienne.taylor@uclouvain.be
- Site Name
- Antwerp University Hospital
- Department Name
- Multidisciplinair Oncologisch Centrum Antwerpen
- Principal Investigator Name
- Konstantinos Papadimitriou
- Principal Investigator Email
- konstantinos.papadimitriou@uza.be
- Contact Person Name
- Konstantinos Papadimitriou
- Contact Person Email
- konstantinos.papadimitriou@uza.be
- Site Name
- Algemeen Ziekenhuis Groeninge
- Department Name
- Kankercentrum: medische oncologie
- Principal Investigator Name
- Laure Nuytemans
- Principal Investigator Email
- laure.nuytemans@azgroeninge.be
- Contact Person Name
- Laure Nuytemans
- Contact Person Email
- laure.nuytemans@azgroeninge.be
- Site Name
- Centre hospitalier universitaire de Liege
- Department Name
- Centre Multidisciplinaire d’Onocologie Médicale
- Principal Investigator Name
- Andree Rorive
- Principal Investigator Email
- andree.rorive@chuliege.be
- Contact Person Name
- Andree Rorive
- Contact Person Email
- andree.rorive@chuliege.be
- Site Name
- Institut Jules Bordet
- Department Name
- Medical oncology department
- Principal Investigator Name
- Andrea Gombos
- Principal Investigator Email
- andrea.gombos@bordet.be
- Contact Person Name
- Andrea Gombos
- Contact Person Email
- andrea.gombos@bordet.be
- Site Name
- UZ Leuven
- Department Name
- Algemene medische oncologie
- Principal Investigator Name
- Hans Wildiers
- Principal Investigator Email
- hans.wildiers@uzleuven.be
- Contact Person Name
- Hans Wildiers
- Contact Person Email
- hans.wildiers@uzleuven.be
Spain
- Latest Decision Or Authorization Date
- 18-07-2024
- Number Of Sites
- 8
- Number Of Participants
- 25
Sites
- Site Name
- University Hospital Son Espases
- Department Name
- Servicio de Oncologia
- Principal Investigator Name
- Neus Ferrer Tur
- Principal Investigator Email
- nieves.ferrer@ssib.es
- Contact Person Name
- Neus Ferrer Tur
- Contact Person Email
- nieves.ferrer@ssib.es
- Site Name
- Hospital Clinico Universitario De Valencia
- Department Name
- Materno Infantil - Servicio Oncologia
- Principal Investigator Name
- Begona Bermejo
- Principal Investigator Email
- begobermejo@gmail.com
- Contact Person Name
- Begona Bermejo
- Contact Person Email
- begobermejo@gmail.com
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Head, Breast Cancer and Melanoma Unit
- Principal Investigator Name
- Cristina Saura Manich
- Principal Investigator Email
- csaura@vhio.net
- Contact Person Name
- Cristina Saura Manich
- Contact Person Email
- csaura@vhio.net
- Site Name
- Hospital Unviersitario Miguel Servet
- Department Name
- Medical Oncology
- Principal Investigator Name
- Antonio Anton Torres
- Principal Investigator Email
- aantont@gmail.com
- Contact Person Name
- Antonio Anton Torres
- Contact Person Email
- aantont@gmail.com
- Site Name
- Hospital Clinico San Carlos
- Department Name
- Servicio de Oncologia Medica
- Principal Investigator Name
- Jose Garcia Saenz
- Principal Investigator Email
- jgsaenz@salud.madrid.org
- Contact Person Name
- Jose Garcia Saenz
- Contact Person Email
- jgsaenz@salud.madrid.org
- Site Name
- Consorci Sanitari Integral
- Department Name
- Hospital Moises Broggi - Servicio Oncologia
- Principal Investigator Name
- Rafael Villanueva Vazquez
- Principal Investigator Email
- ravillanueva@iconcologia.net
- Contact Person Name
- Rafael Villanueva Vazquez
- Contact Person Email
- ravillanueva@iconcologia.net
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- Servicio Oncologia
- Principal Investigator Name
- Manuel Ruiz Borrego
- Principal Investigator Email
- ruizsabater@gmail.com
- Contact Person Name
- Manuel Ruiz Borrego
- Contact Person Email
- ruizsabater@gmail.com
- Site Name
- Hospital Universitario Hm Sanchinarro
- Department Name
- Centro Integral Oncologico Clara Campal
- Principal Investigator Name
- Eva Ciruelos Gil
- Principal Investigator Email
- eva.ciruelos@gmail.com
- Contact Person Name
- Eva Ciruelos Gil
- Contact Person Email
- eva.ciruelos@gmail.com
Denmark
- Latest Decision Or Authorization Date
- 21-07-2024
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- Region Hovedstaden
- Department Name
- Deptartment of Oncology
- Principal Investigator Name
- Eva Harder Brix
- Principal Investigator Email
- eva.harder.brix@regionh.dk
- Contact Person Name
- Eva Harder Brix
- Contact Person Email
- eva.harder.brix@regionh.dk
- Site Name
- Lillebaelt Hospital
- Department Name
- Deptartment of Oncology
- Principal Investigator Name
- Else Iversen
- Principal Investigator Email
- else.iversen@rsyd.dk
- Contact Person Name
- Else Iversen
- Contact Person Email
- else.iversen@rsyd.dk
Germany
- Latest Decision Or Authorization Date
- 22-07-2024
- Number Of Sites
- 4
- Number Of Participants
- 6
Sites
- Site Name
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
- Department Name
- III. Medizinische Klinik und Poliklinik - Haematologie und Medizinische Onkologie
- Principal Investigator Name
- Marcus Schmidt
- Principal Investigator Email
- marcus.schmidt@unimedizin-mainz.de
- Contact Person Name
- Marcus Schmidt
- Contact Person Email
- marcus.schmidt@unimedizin-mainz.de
- Site Name
- Universitaetsklinikum Schleswig-Holstein AöR
- Department Name
- Klinik fur Innere Medizin II, Hamatologie und internistische Onkologie
- Principal Investigator Name
- Marion Van Mackelenbergh
- Principal Investigator Email
- marion.vanmackelenbergh@uksh.de
- Contact Person Name
- Marion Van Mackelenbergh
- Contact Person Email
- marion.vanmackelenbergh@uksh.de
- Site Name
- Institut Fuer Versorgungsforschung In Der Onkologie GbR
- Department Name
- InVO- Institut fur Versorgungsforschung in der Onkologie GbR
- Principal Investigator Name
- Rudolf Weide
- Principal Investigator Email
- weide@invo-koblenz.de
- Contact Person Name
- Rudolf Weide
- Contact Person Email
- weide@invo-koblenz.de
- Site Name
- Klinikum rechts der Isar der TU Muenchen AöR
- Department Name
- Klinik und Poliklinik für Frauenheilkunde
- Principal Investigator Name
- Franziska Kotzur
- Principal Investigator Email
- franziska.kotzur@mri.tum.de
- Contact Person Name
- Franziska Kotzur
- Contact Person Email
- franziska.kotzur@mri.tum.de
Italy
- Latest Decision Or Authorization Date
- 05-08-2024
- Number Of Sites
- 1
- Number Of Participants
- 5
Sites
- Site Name
- Istituto Europeo Di Oncologia S.r.l.
- Department Name
- Divisione di Senologia Medica
- Principal Investigator Name
- Marco Colleoni
- Principal Investigator Email
- marco.colleoni@ieo.it
- Contact Person Name
- Marco Colleoni
- Contact Person Email
- marco.colleoni@ieo.it
Netherlands
- Latest Decision Or Authorization Date
- 05-08-2024
- Number Of Sites
- 3
- Number Of Participants
- 4
Sites
- Site Name
- Amphia Hospital
- Department Name
- Oncology Center: Breast Cancer
- Principal Investigator Name
- Joan Heijns
- Principal Investigator Email
- JHeijns@amphia.nl
- Contact Person Name
- Joan Heijns
- Contact Person Email
- JHeijns@amphia.nl
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- Internal Oncology
- Principal Investigator Name
- Agnes Jager
- Principal Investigator Email
- a.jager@erasmusmc.nl
- Contact Person Name
- Agnes Jager
- Contact Person Email
- a.jager@erasmusmc.nl
- Site Name
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Department Name
- Department of Medical
- Principal Investigator Name
- Gabe Sonke
- Principal Investigator Email
- g.sonke@nki.nl
- Contact Person Name
- Gabe Sonke
- Contact Person Email
- g.sonke@nki.nl
France
- Latest Decision Or Authorization Date
- 13-08-2024
- Number Of Sites
- 10
- Number Of Participants
- 39
Sites
- Site Name
- Oncopole Claudius Regaud
- Department Name
- Oncologie Medicale
- Principal Investigator Name
- Mony Ung
- Principal Investigator Email
- ung.mony@iuct-oncopole.fr
- Contact Person Name
- Mony Ung
- Contact Person Email
- ung.mony@iuct-oncopole.fr
- Site Name
- Centre Francois Baclesse
- Department Name
- Service Oncologie
- Principal Investigator Name
- George Emile
- Principal Investigator Email
- g.emile@baclesse.unicancer.fr
- Contact Person Name
- George Emile
- Contact Person Email
- g.emile@baclesse.unicancer.fr
- Site Name
- Institut Curie
- Department Name
- Oncologie Medicale
- Principal Investigator Name
- Delphine Loirat
- Principal Investigator Email
- delphine.loirat@curie.fr
- Contact Person Name
- Delphine Loirat
- Contact Person Email
- delphine.loirat@curie.fr
- Site Name
- Clinique Victor Hugo
- Department Name
- Oncologie Medicale
- Principal Investigator Name
- Alice Delafoy
- Principal Investigator Email
- essaisdelafoy@ilcgroupe.fr
- Contact Person Name
- Alice Delafoy
- Contact Person Email
- essaisdelafoy@ilcgroupe.fr
- Site Name
- CHU Besancon
- Department Name
- Service Oncologie
- Principal Investigator Name
- Elsa Curtit
- Principal Investigator Email
- elsa.curtit@univ-fcomte.fr
- Contact Person Name
- Elsa Curtit
- Contact Person Email
- elsa.curtit@univ-fcomte.fr
- Site Name
- Centre Hospitalier Regional Universitaire De Tours
- Department Name
- Hematologie et Therapie Cellulaire
- Principal Investigator Name
- Marie-Agnes By
- Principal Investigator Email
- ma.by@chu-tours.fr
- Contact Person Name
- Marie-Agnes By
- Contact Person Email
- ma.by@chu-tours.fr
- Site Name
- Centre Leon Berard
- Department Name
- Cancerologie Medicale
- Principal Investigator Name
- Thomas Bachelot
- Principal Investigator Email
- thomas.bachelot@lyon.unicancer.fr
- Contact Person Name
- Thomas Bachelot
- Contact Person Email
- thomas.bachelot@lyon.unicancer.fr
- Site Name
- Centr Georges Francois Leclerc
- Department Name
- Departement d'Oncologie Medicale
- Principal Investigator Name
- Isabelle Desmoulins
- Principal Investigator Email
- IDesmoulins@cgfl.fr
- Contact Person Name
- Isabelle Desmoulins
- Contact Person Email
- IDesmoulins@cgfl.fr
- Site Name
- Institut Paoli Calmettes
- Department Name
- Service Oncologie
- Principal Investigator Name
- Frederic Viret
- Principal Investigator Email
- viretf@ipc.unicancer.fr
- Contact Person Name
- Frederic Viret
- Contact Person Email
- viretf@ipc.unicancer.fr
- Site Name
- Centre Regional Lutte Contre Le Cancer
- Department Name
- Oncologie Medicale
- Principal Investigator Name
- Thierry Petit
- Principal Investigator Email
- t.petit@icans.eu
- Contact Person Name
- Thierry Petit
- Contact Person Email
- t.petit@icans.eu
Sponsor
Primary sponsor
- Full Name
- Seagen Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Parexel International (IRL) Limited
- Responsibilities
- Monitoring, Medical monitoring and Pharmacovigilance
- Name
- Icon Clinical Research Limited
- Responsibilities
- Sample management (receipt, shipment and storage)
- Name
- Icon Laboratory Services Inc.
- Responsibilities
- Central lab (kit build, sample management, storage and collection of local lab data)
- Name
- Clario
- Responsibilities
- Medical image analysis/ review - Primary/surrogate endpoint test
Third parties
- {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Monitoring, Medical monitoring and Pharmacovigilance; (contact: ichin.chung@parexel.com)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Subject reimbursement; (contact: abiola.ojuade@scoutclinical.com)","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"France","full_name":"Novasco","duties_or_roles":"Subject Reimbursement; (contact: c.maudet@novasco.fr)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Subject Reimbursement; (contact: samantha.moyer@greenphire.com)","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"IVRS – treatment randomisation; (contact: ssannicolas@suvoda.com)","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Data platform/vendor (sponsor duty code listed); (contact: rachel.johnson@3ds.com)","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Clario","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc.; (contact: jahnavi.vyas@clario.com)","organisation_type":"Health care"}
- {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Central lab (Kit build, sample management, storage and collection of local lab data); (contact: Benjamin.Haibach@iconplc.com)","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Sample management (receipt, shipment and storage); (contact: Charl.Schoeman@iconplc.com)","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- TUKYSA 150 mg film-coated tablets
- Active Substance
- Tucatinib
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- oral
- Authorisation Status
- Marketing authorisation (EU) PRD8771193 / EU/1/20/1526/002
- Starting Dose
- 300 mg PO BID (trial experimental arm)
- Dose Levels
- 150 mg (available tablet strength); trial dosing uses 300 mg PO BID (two 150 mg tablets BID)
- Frequency
- BID
- Maximum Dose
- 600 mg/day (product maxDailyDoseAmount 600 mg)
- Investigational Product Name
- TUKYSA 50 mg film-coated tablets
- Active Substance
- Tucatinib
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- oral
- Authorisation Status
- Marketing authorisation (EU) PRD8771172 / EU/1/20/1526/001
- Starting Dose
- 300 mg PO BID (trial experimental arm)
- Dose Levels
- 50 mg (available tablet strength); trial dosing uses 300 mg PO BID
- Frequency
- BID
- Maximum Dose
- 600 mg/day
- Investigational Product Name
- Kadcyla 160 mg powder for concentrate for solution for infusion.
- Active Substance
- Trastuzumab emtansine (T-DM1)
- Modality
- ADC
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- intravenous infusion
- Authorisation Status
- Marketing authorisation (EU) PRD974895 / EU/1/13/885/002
- Starting Dose
- 3.6 mg/kg IV every 21 days (per arm description)
- Dose Levels
- 3.6 mg/kg IV q21 days
- Frequency
- Every 21 days
- Maximum Dose
- 3.6 mg/kg per administration
- Investigational Product Name
- Tucatinib 50mg placebo tablets / Tucatinib 150mg placebo tablets
- Active Substance
- N/A (placebo)
- Modality
- Other
- Starting Dose
- Placebo given PO BID in control arm
- Dose Levels
- Placebo matching 50 mg and 150 mg tablet forms
- Frequency
- BID
- Combination Treatment
- Yes
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