Clinical trial • Phase III | Phase IV • Oncology
trastuzumab deruxtecan for HER2-positive breast cancer | Brain metastases
Phase III | Phase IV trial of trastuzumab deruxtecan for HER2-positive breast cancer | Brain metastases. open-label. 105 participants.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- HER2-positive breast cancer | Brain metastases
- Trial Stage
- Phase III | Phase IV
- Drug Modality
- ADC
Key dates
- Initial CTIS Submission Date
- 17-07-2024
- First CTIS Authorization Date
- 18-09-2024
Trial design
open-label Phase III | Phase IV trial in Belgium, Denmark, Germany and others.
- Open Label
- Yes
- Target Sample Size
- 105
Eligibility
Recruits 105 Vulnerable population selected (isVulnerablePopulationSelected = true). Country-specific informed consent forms and addenda are provided (multiple country ICFs listed across countries/languages). No assent procedures for minors or specific consent-for-minors language are present in the provided data..
- Vulnerable Population
- Vulnerable population selected (isVulnerablePopulationSelected = true). Country-specific informed consent forms and addenda are provided (multiple country ICFs listed across countries/languages). No assent procedures for minors or specific consent-for-minors language are present in the provided data.
Inclusion criteria
- {"criterion_text":"- Pathologically documented breast cancer that: (a) Is unresectable/advanced or metastatic, and (b) Has confirmed HER2-positive status as determined according to ASCO/CAP guidelines (Wolff et al, 2018) evaluated at a local laboratory"}
- {"criterion_text":"- Participant must have either: (a) No evidence of BM, or (b) Untreated BM on screening contrast brain MRI / CT scan (i)not needing immediate local therapy, or (ii)For participants with untreated CNS lesions: - if lesion ≤ 2 cm, no discussion with study physician is required prior to enrollment- if lesion is > 2.0 cm, discussion with and approval from the study physician is required prior to enrollment, or (c) Previously treated stable or progressing BM (i) Previously treated BM with local therapy may either be radiographically stable for ≥ 4 weeks since completion of treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy (ii) Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI/CT scan performed during screening for this study who also have other sites of disease assessable by RECIST 1.1"}
- {"criterion_text":"- Participants with BMs must be neurologically stable and: (a) Be receiving the equivalent of dexamethasone ≤ 3 mg/day if treatment is required (b) If receiving an anticonvulsant regimen, the regimen must have been stable for ≥ 14 days before first day of dosing (c) Relevant records of any CNS treatment must be available to allow for classification of TLs and NTLs"}
- {"criterion_text":"- Previous breast cancer treatment: (a) Radiologic or objective evidence of disease progression on or after HER2 targeted therapies. Note: Disease progression within 6 months after adjuvant treatment with HER2 targeted therapies is also acceptable. (b) No more than 2 lines/regimens of therapy in the metastatic setting. Note: A line/regimen of treatment should be counted based on a progression event."}
Exclusion criteria
- {"criterion_text":"- Known or suspected LMD"}
- {"criterion_text":"- Prior exposure to tucatinib treatment"}
- {"criterion_text":"- Based on screening contrast brain MRI/ CT scan, participants must not have any of the following: (a) Any untreated brain lesions > 2.0 cm in size (b) Ongoing use of systemic corticosteroids for control of symptoms of BMs at a total daily dose of > 3 mg of dexamethasone (or equivalent). (c) Any brain lesion thought to require immediate local therapy, (d) Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to BMs notwithstanding CNS-directed therapy"}
- {"criterion_text":"- Has spinal cord compression"}
Endpoints
Primary endpoints
- {"endpoint_text":"- •Participants without BM at baseline (Cohort 1): ORR by RECIST 1.1 per ICR • Participants with BM at baseline (Cohort 2): PFS by RECIST 1.1 per ICR","definition_or_measurement_approach":"For Cohort 1: Objective Response Rate (ORR) assessed by RECIST 1.1 as adjudicated by Independent Central Review (ICR). For Cohort 2: Progression-Free Survival (PFS) assessed by RECIST 1.1 as adjudicated by ICR."}
Secondary endpoints
- {"endpoint_text":"- • Both cohorts: - OS; - DoR (RECIST ICR); - Time to progression (RECIST ICR); - DoT on subsequent therapy lines; - PFS2. • Cohort 1 only: - Incidence of new symptomatic CNS metastasis during treatment. • In patients with isolated CNS progression, receive local therapy, and continue on protocol therapy: - Time to next progression (CNS or extracranial) or death; - Site (CNS vs extracranial vs both) of next progression.","definition_or_measurement_approach":"OS = Overall Survival; DoR, Time to progression measured by RECIST 1.1 as adjudicated by ICR; DoT = Duration of Treatment on subsequent lines; PFS2 = second progression-free survival. Incidence of symptomatic CNS metastasis captured clinically during treatment; time to next progression and site of next progression recorded per protocol assessments."}
- {"endpoint_text":"- Participants with BM at baseline (Cohort 2): - ORR by RECIST 1.1 per ICR; - CNS PFS by CNS RECIST 1.1 per ICR; - Time to new CNS lesions; - CNS ORR by CNS RECIST 1.1 per ICR; - CNS DoR by CNS RECIST 1.1 per ICR","definition_or_measurement_approach":"ORR and CNS-specific endpoints assessed by CNS RECIST 1.1 and RECIST 1.1 as adjudicated by ICR; time to new CNS lesions measured from baseline to first occurrence of new CNS lesions."}
- {"endpoint_text":"- Changes in symptoms, functioning, and HRQoL as measured by • All patients: EORTC QLQ-C30, NANO scale, cognitive tests. • BM patients: MDASI brain tumor-specific items. • ILD/pneumonitis patients: SGRQ-I","definition_or_measurement_approach":"Patient-reported outcomes and scales: EORTC QLQ-C30, NANO neurological assessment, cognitive tests, MDASI brain tumor items for BM patients, and SGRQ-I for ILD/pneumonitis; changes measured relative to baseline per instrument scoring rules."}
- {"endpoint_text":"- Safety and tolerability will be evaluated in terms of AEs, vital signs, clinical laboratory results, and ECGs, rate of investigator-assessed ILD/pneumonitis, and rate of AEs among patients with baseline BM who are treated with concurrent high-dose steroid (total daily dose > 2 mg dexamethasone or equivalent)","definition_or_measurement_approach":"Safety assessed by adverse events (AEs), vital signs, labs, ECGs; ILD/pneumonitis rates assessed by investigator; special safety subgroup analysis for patients on high-dose steroids (>2 mg dexamethasone or equivalent)."}
Recruitment
- Planned Sample Size
- 105
- Recruitment Window Months
- 71
- Consent Approach
- Informed consent obtained via country-specific informed consent forms. Multiple country ICFs and language versions are provided (examples: English, Spanish, Portuguese, Polish, Dutch, Italian, German, French) including addenda and screening/other specific ICF documents. Functional sponsor contact and country-level ICFs are listed. No assent for minors or minor-specific consent documents are present in the provided data.
Geography
- Total Number Of Sites
- 22
- Total Number Of Participants
- 482
Belgium
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 16-03-2026
- Processing Time Days
- 585
- Number Of Sites
- 2
- Number Of Participants
- 33
Sites
- Site Name
- Institut Jules Bordet
- Department Name
- 0501: Clinique d'Oncologie Médicale
- 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
- Centre hospitalier universitaire de Liege
- Department Name
- 0503: Oncologie Médicale
- Principal Investigator Name
- Joëlle Collignon
- Principal Investigator Email
- joelle.collignon@chuliege.be
- Contact Person Name
- Joëlle Collignon
- Contact Person Email
- joelle.collignon@chuliege.be
Denmark
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 23-05-2025
- Processing Time Days
- 288
- Number Of Sites
- 1
- Number Of Participants
- 5
Sites
- Site Name
- Hillerod Hospital
- Department Name
- 2003: 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
Germany
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 13-03-2026
- Processing Time Days
- 582
- Number Of Sites
- 3
- Number Of Participants
- 48
Sites
- Site Name
- Medizinische Hochschule Hannover
- Department Name
- 2608: Gynäkologische Onkologie
- Principal Investigator Name
- Tjoung-Won Park-Simon
- Principal Investigator Email
- Park-Simon.Tjoung-Won@mh-hannover.de
- Contact Person Name
- Tjoung-Won Park-Simon
- Contact Person Email
- Park-Simon.Tjoung-Won@mh-hannover.de
- Site Name
- Rotkreuzklinikum Muenchen gGmbH
- Department Name
- 2610: Gynäkologie,Brustzentrum
- Principal Investigator Name
- Michael Braun
- Principal Investigator Email
- michael.braun@swmbrk.de
- Contact Person Name
- Michael Braun
- Contact Person Email
- michael.braun@swmbrk.de
- Site Name
- Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
- Department Name
- 2601: Frauenheilkunde, Geburtshilfe
- Principal Investigator Name
- Pauline Wimberger
- Principal Investigator Email
- pauline.wimberger@ukdd.de
- Contact Person Name
- Pauline Wimberger
- Contact Person Email
- pauline.wimberger@ukdd.de
Ireland
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 18-09-2024
- Processing Time Days
- 41
- Number Of Sites
- 3
- Number Of Participants
- 33
Sites
- Site Name
- Mater Misericordiae University Hospital
- Department Name
- 3901: Oncology
- Principal Investigator Name
- John McCaffrey
- Principal Investigator Email
- jmccaffrey@mater.ie
- Contact Person Name
- John McCaffrey
- Contact Person Email
- jmccaffrey@mater.ie
- Site Name
- Cork University Hospital
- Department Name
- 3902 :Oncology
- Principal Investigator Name
- Roisin Connolly
- Principal Investigator Email
- roisin.connolly5@hse.ie
- Contact Person Name
- Roisin Connolly
- Contact Person Email
- roisin.connolly5@hse.ie
- Site Name
- St Vincent's University Hospital
- Department Name
- 3903: Oncology
- Principal Investigator Name
- Michaela Higgins
- Principal Investigator Email
- michaelahiggins@svhg.ie
- Contact Person Name
- Michaela Higgins
- Contact Person Email
- michaelahiggins@svhg.ie
Italy
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 13-03-2026
- Processing Time Days
- 582
- Number Of Sites
- 5
- Number Of Participants
- 114
Sites
- Site Name
- Ospedale San Raffaele S.r.l.
- Department Name
- 4107: 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
- Humanitas Istituto Clinico Catanese S.p.A.
- Department Name
- 4103: NA
- Principal Investigator Name
- Michele Caruso
- Principal Investigator Email
- michele.caruso@ccocatania.it
- Contact Person Name
- Michele Caruso
- Contact Person Email
- michele.caruso@ccocatania.it
- Site Name
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Department Name
- 4101: S.C. Oncologia Medica Senologia
- Principal Investigator Name
- Michelino De Laurentiis
- Principal Investigator Email
- delauren@breastunit.org
- Contact Person Name
- Michelino De Laurentiis
- Contact Person Email
- delauren@breastunit.org
- Site Name
- Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
- Department Name
- 4106:Oncologia
- Principal Investigator Name
- Vittoria Fotia
- Principal Investigator Email
- vfotia@asst-pg23.it
- Contact Person Name
- Vittoria Fotia
- Contact Person Email
- vfotia@asst-pg23.it
- Site Name
- Istituto Oncologico Veneto
- Department Name
- 4102: UO Oncologia Medica II
- Principal Investigator Name
- Valentina Guarneri
- Principal Investigator Email
- valentina.guarneri@unipd.it
- Contact Person Name
- Valentina Guarneri
- Contact Person Email
- valentina.guarneri@unipd.it
Poland
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 16-03-2026
- Processing Time Days
- 585
- Number Of Sites
- 5
- Number Of Participants
- 89
Sites
- Site Name
- Opolskie Centrum Onkologii Im. Prof. Tadeusza Koszarowskiego W Opolu Samodzielny Publiczny Zaklad Opieki Zdrowotnej
- Department Name
- 5703:Oddzial Onkologii Klinicznej z Odcinkiem Dziennym
- Principal Investigator Name
- Barbara Radecka
- Principal Investigator Email
- brad@onkologia.opole.pl
- Contact Person Name
- Barbara Radecka
- Contact Person Email
- brad@onkologia.opole.pl
- Site Name
- Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
- Department Name
- 5705:Klinika Onkologii
- Principal Investigator Name
- Renata Duchnowska
- Principal Investigator Email
- rdtt@wp.pl
- Contact Person Name
- Renata Duchnowska
- Contact Person Email
- rdtt@wp.pl
- Site Name
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie
- Department Name
- 5701:Oddzial Kliniczny Onkologii
- Principal Investigator Name
- Piotr Wysocki
- Principal Investigator Email
- piotr.wysocki@uj.edu.pl
- Contact Person Name
- Piotr Wysocki
- Contact Person Email
- piotr.wysocki@uj.edu.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- 5704:Klin. Onkologii i Radioterapii
- Principal Investigator Name
- Jacek Jassem
- Principal Investigator Email
- jjassem@gumed.edu.pl
- Contact Person Name
- Jacek Jassem
- Contact Person Email
- jjassem@gumed.edu.pl
- Site Name
- Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
- Department Name
- 5702:Klinika Nowotworow Piersi i Chirurgii Rekonstrukcyjnej
- Principal Investigator Name
- Zbigniew Nowecki
- Principal Investigator Email
- Zbigniew.Nowecki@pib-nio.pl
- Contact Person Name
- Zbigniew Nowecki
- Contact Person Email
- Zbigniew.Nowecki@pib-nio.pl
Portugal
- Earliest CTIS Part Ii Submission Date
- 08-08-2024
- Latest Decision Or Authorization Date
- 12-03-2026
- Processing Time Days
- 581
- Number Of Sites
- 2
- Number Of Participants
- 17
Sites
- Site Name
- Champalimaud Clinical Centre
- Department Name
- 5802:Unidade de Mama
- Principal Investigator Name
- Márcio Debiasi
- Principal Investigator Email
- marcio.debiasi@fundacaochampalimaud.pt
- Contact Person Name
- Márcio Debiasi
- Contact Person Email
- marcio.debiasi@fundacaochampalimaud.pt
- Site Name
- Hospital De Santa Maria E.P.E.
- Department Name
- 5803:Oncologia
- Principal Investigator Name
- Ana Rita Sousa
- Principal Investigator Email
- ana.r.sousa@chln.min-saude.pt
- Contact Person Name
- Ana Rita Sousa
- Contact Person Email
- ana.r.sousa@chln.min-saude.pt
Sponsor
Primary sponsor
- Full Name
- AstraZeneca AB
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Sweden
Contract research organisations
- Name
- Parexel International (IRL) Limited
- Responsibilities
- Sponsor duties codes: 1,10,11,12,13,2,5,6,7,8,9; contact Clinicaltrial.Enquiries@parexel.com; phone +35314739500
Third parties
- {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"1,10,11,12,13,2,5,6,7,8,9","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- DS-8201a
- Active Substance
- trastuzumab deruxtecan
- Modality
- ADC
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Authorised (EU product PRD5308994; MIA number provided)
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