Clinical trial • Phase III • Oncology
TRASTUZUMAB DERUXTECAN for HER2-positive early-stage breast cancer
Phase III trial of TRASTUZUMAB DERUXTECAN for HER2-positive early-stage breast cancer.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- HER2-positive early-stage breast cancer
- Trial Stage
- Phase III
- Drug Modality
- ADC|Monoclonal antibody|Small molecule
Key dates
- Initial CTIS Submission Date
- 20-08-2024
- First CTIS Authorization Date
- 01-10-2024
Trial design
Randomised, open-label, ddac-thp (doxorubicin and cyclophosphamide, followed by thp). dose and schedule not specified in the available source.-controlled Phase III trial across 35 sites in Germany, Poland, Italy and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- ddAC-THP (doxorubicin and cyclophosphamide, followed by THP). Dose and schedule not specified in the available source.
- Target Sample Size
- 630
Eligibility
Recruits 630 adults.
Inclusion criteria
- {"criterion_text":"- Patients must be at least 18 years of age.\n- Histologically documented HER2-positive EBC participants with: (a) Locally assessed HER2-positive (IHC 3+ or ISH+) according to ASCO-CAP guidelines and prospectively centrally confirmed as HER2 positive based on a tumour sample (b) Unifocal and multifocal tumours (> 1 tumour confined to the same quadrant as the primary tumour) must have 1 focus sampled and centrally confirmed as HER2 positive (c) Multi-centric tumours (multiple tumours involving > 1 quadrant of the breast) must have 1 lesion from each involved quadrant sampled and centrally confirmed as HER2 positive. All quadrants tested must be centrally confirmed as HER2 positive (d) Tumours documented as HR-positive (either ER and/or PgR positive [ER or PgR ≥ 1%]) or HR-negative (ER and PgR negative) by local assessment per ASCO-CAP guidelines (Allison et al 2020) (e) Clinical stage at presentation (based on mammogram or breast MRI assessment): T0-4 (inclusive of inflammatory breast cancer), N1-3, M0 or ≥ T3, N0, M0 as determined by the AJCC staging system, 8th edition (Hortobagyi et al 2017) (f) Pathologic confirmation of nodal involvement with malignancy as determined by fine-needle aspiration or core-needle biopsy, when applicable.\n- FFPE tissue block (2 cores) or 20 freshly-cut, serial tumor slides for HER2 assessment by central lab. If blocks are incomplete or fewer than 20 slides are available, participants may be eligible following discussion with the AstraZeneca Study Physician\n- ECOG performance status of 0 or 1 at randomization\n- Adequate organ and bone marrow function\n- LVEF ≥ 50% within 28 days before randomization"}
Exclusion criteria
- {"criterion_text":"- Prior history of invasive breast cancer\n- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any pulmonary disorder\n- Investigator judgement of 1 or more of the following: (a) Mean resting corrected QTcF interval of >470 ms (females) or >450 ms (males) (b) History of QT prolongation associated with other medications that required discontinuation of that medication or any medication known to prolong QT interval and cause TdP. (c) Congenital long QT syndrome, family history of long QT syndrome or unexplained death under 40 years in first degree relatives\n- History of arrhythmia, symptomatic or uncontrolled atrial fibrillation or asymptomatic sustained ventricular tachycardia\n- Any primary malignancy within 3 years, except adequately resected non-melanoma skin cancer, or curatively treated in situ disease Note: This includes a second current breast primary malignancy (ie, bilateral breast cancer)\n- History of DCIS, except for participants treated with mastectomy only > 5 years prior to current diagnosis\n- Prior sentinel lymph node biopsy or axillary lymph node dissection before initiation of neoadjuvant treatment\n- Prior systemic therapy for the treatment of breast cancer\n- Previous treatment with anthracyclines, cyclophosphamide or taxanes for any malignancy; cyclophosphamide allowed for non-cancer treatment if last dose > 6 months\n- Ineligible for any medication in the control Arm C\n- Any concurrent anticancer treatment\n- History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening"}
Endpoints
Primary endpoints
- {"endpoint_text":"- pCR (ypT0/Tis ypN0): Rate of pCR is defined as the proportion of participants who have no evidence by H&E staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy.","definition_or_measurement_approach":"Rate of pCR is defined as the proportion of participants who have no evidence by H&E staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy."}
Secondary endpoints
- {"endpoint_text":"- pCR (ypT0 ypN0): Rate of pCR is defined as the proportion of participants who have no evidence by H&E staining of residual invasive disease and in situ cancer in the complete resected breast specimen and all sampled regional lymph nodes (ypT0 ypN0) following completion of neoadjuvant therapy.","definition_or_measurement_approach":"Rate of pCR defined as proportion with no evidence by H&E staining of residual invasive disease and in situ cancer in resected breast specimen and sampled regional lymph nodes (ypT0 ypN0) after neoadjuvant therapy."}
- {"endpoint_text":"- EFS","definition_or_measurement_approach":"Event-free survival (EFS) as specified in protocol (3-year EFS assessed as a secondary objective)."}
- {"endpoint_text":"- IDFS","definition_or_measurement_approach":"Invasive-disease free survival (IDFS) as specified in protocol (3-year IDFS assessed as a secondary objective)."}
- {"endpoint_text":"- OS","definition_or_measurement_approach":"Overall survival (OS) as specified in protocol."}
- {"endpoint_text":"- HRQoL: Symptomatic AEs assessed by the PRO-CTCAE and items from the EORTC Item Library. Overall side-effect bother measured by PGI-TT at each time point in each treatment arm. Physical function assessed by the EORTC QLQ-C30 Physical Function Scale.","definition_or_measurement_approach":"Symptomatic adverse events assessed by PRO-CTCAE and EORTC items; PGI-TT used to measure overall side-effect bother; EORTC QLQ-C30 Physical Function Scale for physical function."}
- {"endpoint_text":"- Safety and Tolerability: Occurrence of AEs, SAEs and changes from baseline in vital signs, clinical laboratory results, ECGs, and ECHO/MUGA. Heart failure evaluated by the percentage of participants with NYHA Class III and IV heart failure. Decreases in LVEF (requires at least 2 consecutive readings of decline) by percentage of participants with decreases in LVEF of at least 10 points from baseline and to below 50%.","definition_or_measurement_approach":"Safety assessed by occurrence of AEs/SAEs and changes from baseline in vital signs, labs, ECGs, ECHO/MUGA; heart failure by NYHA Class III/IV percentage; LVEF decreases defined as ≥10 point decline and to below 50% (requires ≥2 consecutive readings)."}
- {"endpoint_text":"- PK of T-DXd: Serum concentration of T-DXd, anti-HER2 antibody, and DXd.","definition_or_measurement_approach":"Pharmacokinetics measured by serum concentrations of T-DXd, anti-HER2 antibody, and DXd."}
- {"endpoint_text":"- Immunogenicity for T-DXd: Number and percentage of participants who develop ADAs for T-DXd.","definition_or_measurement_approach":"Immunogenicity assessed by number and percentage of participants developing anti-drug antibodies (ADAs) to T-DXd."}
Recruitment
- Planned Sample Size
- 630
- Recruitment Window Months
- 66
- Consent Approach
- Informed consent obtained from adult participants (participants must be at least 18 years of age). Subject information and informed consent forms are provided for publication in multiple languages (documents include country/language-specific ICFs: Polish, Italian, Spanish, German, and English lay synopsis/I CF documents are listed). An eConsent document is listed for Italy. No information on assent processes (not applicable as study enrolls adults only).
Geography
- Total Number Of Sites
- 35
- Total Number Of Participants
- 280
Germany
- Latest Decision Or Authorization Date
- 28-01-2025
- Number Of Sites
- 12
- Number Of Participants
- 54
Sites
- Site Name
- Mammazentrum Hamburg MVZ GbR
- Department Name
- Mammazentrum
- Contact Person Name
- Christian Schem
- Contact Person Email
- schem@mammazentrum.eu
- Site Name
- Universitaetsklinikum Augsburg
- Department Name
- Frauenklinik
- Contact Person Name
- Nina Ditsch
- Contact Person Email
- nina.ditsch@uk-augsburg.de
- Site Name
- St. Vincenz-Krankenhaus GmbH
- Department Name
- Klinik für Gynäkologie und Geburtshilfe; Kooperatives Brustzentrum Paderborn Gyn. Krebszentrum
- Contact Person Name
- Michael Patrick Lux
- Contact Person Email
- M.Lux@vincenz.de
- Site Name
- Universitaetsklinikum Tuebingen AöR
- Department Name
- Department für Frauengesundheit
- Contact Person Name
- Andreas Hartkopf
- Contact Person Email
- andreas.hartkopf@med.uni-tuebingen.de
- Site Name
- National Center For Tumor Diseases (NCT) Heidelberg
- Department Name
- Nationales Centrum für Tumorerkrankungen Heidelberg
- Contact Person Name
- Andreas Schneeweiss
- Contact Person Email
- andreas.schneeweiss@med.uni-heidelberg.de
- Site Name
- Klinikum der Universitaet Muenchen AöR
- Department Name
- Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
- Contact Person Name
- Nadia Harbeck
- Contact Person Email
- nadia.harbeck@med.uni-muenchen.de
- Site Name
- Universitaetsklinikum Leipzig AöR
- Department Name
- Klinik und Poliklinik für Frauenheilkunde
- Contact Person Name
- Bahriye Aktas
- Contact Person Email
- bahriye.aktas@medizin.uni-leipzig.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Klinik für Gynäkologie mit Brustzentrum
- Principal Investigator Name
- Caroline Neeb
- Principal Investigator Email
- Caroline.neeb@charite.de
- Contact Person Name
- Caroline Neeb
- Contact Person Email
- Caroline.neeb@charite.de
- Site Name
- Universitaetsklinikum Erlangen AöR
- Department Name
- Frauenklinik
- Contact Person Name
- Peter Fasching
- Contact Person Email
- peter.fasching.studien@uk-erlangen.de
- Site Name
- Brustzentrum Rhein-Ruhr Servicegesellschaft mbH
- Department Name
- Brustzentrum Niederrhein
- Principal Investigator Name
- Iris Scheffen
- Principal Investigator Email
- Iris.Scheffen@mg.johanniter-kliniken.de
- Contact Person Name
- Iris Scheffen
- Contact Person Email
- Iris.Scheffen@mg.johanniter-kliniken.de
- Site Name
- Universitaetsklinikum Schleswig-Holstein AöR
- Department Name
- Klinik für Gynäkologie und Geburtshilfe
- Principal Investigator Name
- Marion von Mackelenbergh
- Principal Investigator Email
- MarionTina.vanMackelenbergh@uksh.de
- Contact Person Name
- Marion von Mackelenbergh
- Contact Person Email
- MarionTina.vanMackelenbergh@uksh.de
- Site Name
- Universitaet Muenster
- Department Name
- Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe - Senologie
- Principal Investigator Name
- Joke Tio
- Principal Investigator Email
- joke.tio@ukmuenster.de
- Contact Person Name
- Joke Tio
- Contact Person Email
- joke.tio@ukmuenster.de
Poland
- Latest Decision Or Authorization Date
- 29-01-2025
- Number Of Sites
- 5
- Number Of Participants
- 68
Sites
- Site Name
- Wojewodzki Szpital Specjalistyczny W Bialej Podlaskiej
- Principal Investigator Name
- Piotr Centkowski
- Principal Investigator Email
- pcentek@wp.pl
- Contact Person Name
- Piotr Centkowski
- Contact Person Email
- pcentek@wp.pl
- Site Name
- Bialostockie Centrum Onkologii Im. Marii Sklodowskiej-Curie W Bialymstoku
- Principal Investigator Name
- Bogumiła Czartoryska-Arlukowicz
- Principal Investigator Email
- barlukowicz@poczta.onet.pl
- Contact Person Name
- Bogumiła Czartoryska-Arlukowicz
- Contact Person Email
- barlukowicz@poczta.onet.pl
- Site Name
- Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
- Department Name
- Oddzial Chemioterapii
- Principal Investigator Name
- Bogdan Zurawski
- Principal Investigator Email
- zurawskib@co.bydgoszcz.pl
- Contact Person Name
- Bogdan Zurawski
- Contact Person Email
- zurawskib@co.bydgoszcz.pl
- Site Name
- Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
- Department Name
- Klinika Nowotworow Piersi i Chirurgii Rekonstrukcyjnej
- Principal Investigator Name
- Zbigniew Nowecki
- Principal Investigator Email
- zbigniew.nowecki@nio.gov.pl
- Contact Person Name
- Zbigniew Nowecki
- Contact Person Email
- zbigniew.nowecki@nio.gov.pl
- Site Name
- Centrum Onkologii Ziemi Lubelskiej Im. Sw. Jana Z Dukli
- Principal Investigator Name
- Aneta Dobrzynska-Rutkowska
- Principal Investigator Email
- aneta.rut77@gmail.com
- Contact Person Name
- Aneta Dobrzynska-Rutkowska
- Contact Person Email
- aneta.rut77@gmail.com
Italy
- Latest Decision Or Authorization Date
- 28-01-2025
- Number Of Sites
- 10
- Number Of Participants
- 94
Sites
- Site Name
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Claudio Zamagni
- Principal Investigator Email
- zamagniclaudio.sper@aosp.bo.it
- Contact Person Name
- Claudio Zamagni
- Contact Person Email
- zamagniclaudio.sper@aosp.bo.it
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- Medicina di precisione in senologia
- Principal Investigator Name
- Alessandra Fabi
- Principal Investigator Email
- alessandra.fabi@virgilio.it
- Contact Person Name
- Alessandra Fabi
- Contact Person Email
- alessandra.fabi@virgilio.it
- Site Name
- Ospedale San Raffaele S.r.l.
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Giampaolo Bianchini
- Principal Investigator Email
- bianchini.giampaolo@hsr.it
- Contact Person Name
- Giampaolo Bianchini
- Contact Person Email
- bianchini.giampaolo@hsr.it
- Site Name
- IRCCS Ospedale Sacro Cuore Don Calabria
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Stefania Gori
- Principal Investigator Email
- stefania.gori@sacrocuore.it
- Contact Person Name
- Stefania Gori
- Contact Person Email
- stefania.gori@sacrocuore.it
- Site Name
- Istituto Di Candiolo Fondazione Del Piemonte Per L'Oncologia IRCCS
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Vanessa Gregorc
- Principal Investigator Email
- vanesa.gregorc@ircc.it
- Contact Person Name
- Vanessa Gregorc
- Contact Person Email
- vanesa.gregorc@ircc.it
- Site Name
- Azienda Unita' Sanitaria Locale Toscana Nord Ovest
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Luigi Coltelli
- Principal Investigator Email
- Luigi.coltelli@uslnordovest.toscana.it
- Contact Person Name
- Luigi Coltelli
- Contact Person Email
- Luigi.coltelli@uslnordovest.toscana.it
- Site Name
- Humanitas Mirasole S.p.A.
- Department Name
- Oncologia Medica ed Ematologia
- Principal Investigator Name
- Armando Santoro
- Principal Investigator Email
- armando.santoro@cancercenter.humanitas.it
- Contact Person Name
- Armando Santoro
- Contact Person Email
- armando.santoro@cancercenter.humanitas.it
- Site Name
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Michelino De Laurentiis
- Principal Investigator Email
- m.delaurentiis@istitutotumori.na.it
- Contact Person Name
- Michelino De Laurentiis
- Contact Person Email
- m.delaurentiis@istitutotumori.na.it
- Site Name
- Istituto Oncologico Veneto
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Valentina Guarneri
- Principal Investigator Email
- valentina.guarneri@iov.veneto.it
- Contact Person Name
- Valentina Guarneri
- Contact Person Email
- valentina.guarneri@iov.veneto.it
- Site Name
- Azienda Ospedaliera Universitaria Federico II Di Napoli
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Grazia Arpino
- Principal Investigator Email
- grazia.arpino@unina.it
- Contact Person Name
- Grazia Arpino
- Contact Person Email
- grazia.arpino@unina.it
Spain
- Latest Decision Or Authorization Date
- 13-02-2025
- Number Of Sites
- 8
- Number Of Participants
- 64
Sites
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- Servicio de Oncología
- 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 Universitari Vall D Hebron
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- Santiago Ignacio Escriva de Romani Muñoz
- Principal Investigator Email
- sescriva@vhio.net
- Contact Person Name
- Santiago Ignacio Escriva de Romani Muñoz
- Contact Person Email
- sescriva@vhio.net
- Site Name
- Hospital Universitari Dexeus Grupo Quironsalud
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- Alejandro Martinez Bueno
- Principal Investigator Email
- amartinez@oncorosell.com
- Contact Person Name
- Alejandro Martinez Bueno
- Contact Person Email
- amartinez@oncorosell.com
- Site Name
- Hospital Alvaro Cunqueiro
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- Isabel Lorenzo Lorenzo
- Principal Investigator Email
- isabel.lorenzo.lorenzo@sergas.es
- Contact Person Name
- Isabel Lorenzo Lorenzo
- Contact Person Email
- isabel.lorenzo.lorenzo@sergas.es
- Site Name
- Hospital Clinico San Carlos
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- Jose Angel Garcia Saenz
- Principal Investigator Email
- jgsaenz@salud.madrid.org
- Contact Person Name
- Jose Angel Garcia Saenz
- Contact Person Email
- jgsaenz@salud.madrid.org
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- Miguel Martin Jimenez
- Principal Investigator Email
- mmartin@geicam.org
- Contact Person Name
- Miguel Martin Jimenez
- Contact Person Email
- mmartin@geicam.org
- Site Name
- Hospital Universitario Virgen Del Rocio S.L. (duplicate entry in record)
- Department Name
- Servicio de Oncología
- 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 Universitari Vall D Hebron (duplicate entry in record)
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- Santiago Ignacio Escriva de Romani Muñoz
- Principal Investigator Email
- sescriva@vhio.net
- Contact Person Name
- Santiago Ignacio Escriva de Romani Muñoz
- Contact Person Email
- sescriva@vhio.net
Sponsor
Primary sponsor
- Full Name
- AstraZeneca AB
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Sweden
Investigational products
- Investigational Product Name
- DS-8201a
- Active Substance
- TRASTUZUMAB DERUXTECAN
- Modality
- ADC
- Routes Of Administration
- INTRAVENOUS
- Route
- INTRAVENOUS
- Authorisation Status
- PRD5308994
- Investigational Product Name
- Herzuma 150 mg powder for concentrate for solution for infusion
- Active Substance
- TRASTUZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS
- Route
- INTRAVENOUS
- Authorisation Status
- EU/1/17/1257/001
- Investigational Product Name
- Herzuma 420 mg powder for concentrate for solution for infusion
- Active Substance
- TRASTUZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS
- Route
- INTRAVENOUS
- Authorisation Status
- PRD6684811
- Investigational Product Name
- Perjeta 420 mg concentrate for solution for infusion
- Active Substance
- PERTUZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS
- Route
- INTRAVENOUS
- Authorisation Status
- EU/1/13/813/001
- Investigational Product Name
- PACLITAXEL
- Active Substance
- PACLITAXEL
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS
- Route
- INTRAVENOUS
- Investigational Product Name
- CYCLOPHOSPHAMIDE
- Active Substance
- CYCLOPHOSPHAMIDE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS
- Route
- INTRAVENOUS
- Investigational Product Name
- DOXORUBICIN
- Active Substance
- DOXORUBICIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS
- Route
- INTRAVENOUS
- Combination Treatment
- Yes
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