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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04739761




Registration number
NCT04739761
Ethics application status
Date submitted
20/01/2021
Date registered
5/02/2021

Titles & IDs
Public title
A Study of T-DXd in Participants With or Without Brain Metastasis Who Have Previously Treated Advanced or Metastatic HER2 Positive Breast Cancer
Scientific title
An Open-Label, Multinational, Multicenter, Phase 3b/4 Study of Trastuzumab Deruxtecan in Patients With or Without Baseline Brain Metastasis With Previously Treated Advanced/Metastatic HER2-Positive Breast Cancer (DESTINY-Breast12)
Secondary ID [1] 0 0
2024-510588-53-00
Secondary ID [2] 0 0
D9673C00007
Universal Trial Number (UTN)
Trial acronym
DESTINY-B12
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Trastuzumab Deruxtecan

Experimental: Trastuzumab Deruxtecan - Participants with or without BM at baseline will receive intravenous (IV) T-DXd, 5.4 mg/kg, every 3 weeks (21-day cycle) until Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) defined radiological progression outside central nervous system, unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.


Treatment: Drugs: Trastuzumab Deruxtecan
Participants will receive T-DXd administered using an IV bag containing 5% (w/v) dextrose injection infusion solution.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) in Cohort 1 (Participants Without Brain Metastasis at Baseline)
Timepoint [1] 0 0
From first dose (Day 1) to progression of disease (up to 2 years 7 months)
Primary outcome [2] 0 0
Progression-free Survival (PFS) Rate at 12 Months in Cohort 2 (Participants With Brain Metastasis at Baseline)
Timepoint [2] 0 0
At 12 months
Secondary outcome [1] 0 0
Survival Rate at 12 Months
Timepoint [1] 0 0
At 12 Months
Secondary outcome [2] 0 0
Objective Response Rate in Cohort 2 (Participants With Brain Metastasis at Baseline)
Timepoint [2] 0 0
From first dose (Day 1) to progression of disease (up to 2 years 7 months)
Secondary outcome [3] 0 0
Duration of Response (DoR)
Timepoint [3] 0 0
From the date of first documented confirmed response until date of documented progression (up to 2 years 7 months)
Secondary outcome [4] 0 0
Time to Progression
Timepoint [4] 0 0
From first dose (Day 1) to progression of disease (up to 2 years 7 months)
Secondary outcome [5] 0 0
Duration of Treatment on Subsequent Lines of Therapy
Timepoint [5] 0 0
From the date of first dose of a subsequent therapy until date of last dose of therapy (up to 2 years 7 months)
Secondary outcome [6] 0 0
Second Progression-Free Survival Rate at 12 Months
Timepoint [6] 0 0
At 12 Months
Secondary outcome [7] 0 0
Incidence of New Symptomatic Central Nervous System (CNS) Metastasis During Treatment Without CNS Metastasis at Baseline (Cohort 1)
Timepoint [7] 0 0
From first dose (Day 1) to end of treatment (up to 2 years 7 months)
Secondary outcome [8] 0 0
Time to Next Progression (CNS or Extracranial) or Death
Timepoint [8] 0 0
From date of first documented isolated CNS progression to the date of the next documented disease progression (up to 2 years 7 months)
Secondary outcome [9] 0 0
Site (CNS vs Extracranial vs Both) of Next Progression
Timepoint [9] 0 0
From the date of the first documented isolated CNS progression to the date of the next documented CNS disease progression (up to 2 years 7 months)
Secondary outcome [10] 0 0
Central Nervous System Progression-free Survival Rate at 12 Months in Participants With Brain Metastasis at Baseline (Cohort 2)
Timepoint [10] 0 0
At 12 Months
Secondary outcome [11] 0 0
Time to New CNS Lesions in Participants With Brain Metastasis at Baseline (Cohort 2)
Timepoint [11] 0 0
From first dose (Day 1) to the date of documented new CNS lesions (up to 2 years 7 months)
Secondary outcome [12] 0 0
Central Nervous System Objective Response Rate in Participants With Brain Metastasis at Baseline by ICR (Cohort 2)
Timepoint [12] 0 0
From first dose (Day 1) until CNS progression of disease (up to 2 years 7 months)
Secondary outcome [13] 0 0
Central Nervous System Duration of Response in Participants With Brain Metastasis at Baseline (Cohort 2)
Timepoint [13] 0 0
From date of first documented confirmed CNS response until CNS progression of disease (up to 2 years 7 months)
Secondary outcome [14] 0 0
Number of Participants With Best on Treatment Visit Response on the European Organization for the Research and Treatment of Cancer 30-Item Core Quality of Life Questionnaire (EORTC QLQ-C30)
Timepoint [14] 0 0
Time from first dose up to 47 days after last dose, or prior to starting any subsequent therapy, or for up to 2 years 7 months, whichever occurred first
Secondary outcome [15] 0 0
Number of Participants With Neurologic Assessment in Neuro-Oncology Scale (NANO Scale)
Timepoint [15] 0 0
Time from first dose up to 47 days after last dose, or prior to starting any subsequent therapy, or for up to 2 years 7 months, whichever occurred first
Secondary outcome [16] 0 0
Cognitive Functions Tests: Paired Associates Learning (PAL) First Attempt Memory Score (PALFAMS)
Timepoint [16] 0 0
Baseline, Cycle 5 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, and Cycle 17 Day 1 (21 days cycle)
Secondary outcome [17] 0 0
Cognitive Functions Tests: Paired Associates Learning Total Errors Adjusted (PALTEA)
Timepoint [17] 0 0
Baseline, Cycle 5 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, and Cycle 17 Day 1 (21 days cycle)
Secondary outcome [18] 0 0
Cognitive Functions Tests: Reaction Time (RTI)
Timepoint [18] 0 0
Baseline, Cycle 5 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, and Cycle 17 Day 1 (21 days cycle)
Secondary outcome [19] 0 0
Cognitive Functions Tests: Spatial Working Memory (SWM)
Timepoint [19] 0 0
Baseline, Cycle 5 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, and Cycle 17 Day 1 (21 days cycle)
Secondary outcome [20] 0 0
Cognitive Functions Tests: Spatial Working Memory Strategy (SWMS)
Timepoint [20] 0 0
Baseline, Cycle 5 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, and Cycle 17 Day 1 (21 days cycle)
Secondary outcome [21] 0 0
St. George's Respiratory Questionnaire - Idiopathic (SGRQ-I) Pulmonary Fibrosis Version in Participants With Interstitial Lung Disease (ILD)/Pneumonitis
Timepoint [21] 0 0
From time of ILD/pneumonitis diagnosis (every week) until end of safety follow-up (47 days post last dose) (up to 2 years 7 months)
Secondary outcome [22] 0 0
MD Anderson Symptom Inventory Brain Tumor-Specific Items in Brain Metastasis at Baseline Participants
Timepoint [22] 0 0
Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 39 Day 1 (21 days cycle)
Secondary outcome [23] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [23] 0 0
From first dose until end of safety follow-up (47 days post last dose) (up to 2 years 7 months)
Secondary outcome [24] 0 0
Number of Participants With Investigator-assessed ILD/Pneumonitis
Timepoint [24] 0 0
From first dose until end of safety follow-up (47 days post last dose) (up to 2 years 7 months)
Secondary outcome [25] 0 0
Number of Participants With ILD Clinical Symptoms Resolution Among ILD/Pneumonitis Participants Who Have Been Treated With High Dose Steroid
Timepoint [25] 0 0
From first dose until end of safety follow-up (47 days post last dose) (up to 2 years 7 months)

Eligibility
Key inclusion criteria
Inclusion:

* Participants should have pathologically documented breast cancer that is: unresectable/advanced or metastatic; confirmed HER2-positive status expression as determined according to American Society of Clinical Oncology/College of American Pathologists guidelines
* Participant must have either: no evidence of BM, or untreated BM on screening contrast brain magnetic resonance imaging/ computed tomography (MRI/CT) scan, not needing immediate local therapy or previously-treated stable or progressing BM
* Participants with BMs must be neurologically stable
* For participants requiring radiotherapy due to BMs, there should be an adequate washout period before day of first dosing:
* = 7 days since stereotactic radiosurgery or gamma knife
* = 21 days since whole brain radiotherapy
* Eastern Cooperative Oncology Group performance status 0-1
* Previous breast cancer treatment: radiologic or objective evidence of disease progression on or after HER2 targeted therapies and no more than 2 lines/regimens of therapy in the metastatic setting
* Participant with the following measurable: at least 1 lesion that can be accurately measured at baseline as = 10 mm in the longest diameter with CT or MRI and is suitable for accurate repeated measurements; or following Non-measurable diseases: Non-measurable, bone-only disease that can be assessed by CT or MRI or X-Ray. Lytic or mixed lytic bone lesions that can be assessed by CT or MRI or X-ray in the absence of measurable disease as defined above is acceptable; Participants with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible; and Non-measurable CNS disease (Cohort 2 only)
* Adequate organ and bone marrow function within 14 days before the day of first dosing as defined in the protocol
* Left ventricular ejection fraction = 50% within 28 days before enrollment
* Negative pregnancy test (serum) for women of childbearing potential
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Known or suspected leptomeningeal disease
* Prior exposure to tucatinib treatment
* Refractory nausea and vomiting, chronic gastrointestinal disease, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of T-DXd
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence
* Based on screening contrast brain MRI/CT scan, participants must not have any of the following: any untreated brain lesions > 2.0 cm in size; ongoing use of systemic corticosteroids for control of symptoms of BMs; any brain lesion thought to require immediate local therapy; have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to BMs not withstanding CNS-directed therapy
* Has spinal cord compression
* Known active hepatitis B or C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1. Participants with past or resolved hepatitis B virus infection are eligible, if negative for hepatitis B surface antigen and positive for anti-hepatitis B core antigen
* Participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd
* Participants with a medical history of myocardial infarction within 6 months before screening, symptomatic congestive heart failure (New York Heart Association Class II to IV)
* 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
* Lung-specific intercurrent clinically significant illnesses and any autoimmune, connective tissue or inflammatory disorders
* Prior exposure, without adequate treatment washout period before the day of first dosing, to chloroquine/hydroxychloroquine: < 14 days
* Anticancer chemotherapy: immunotherapy (non-antibody-based therapy), retinoid therapy, hormonal therapy: < 3 weeks
* < 6 weeks for nitrosoureas or mitomycin
* Antibody-based anticancer therapy: < 4 weeks
* Any concurrent anticancer treatment. Concurrent use of hormonal therapy for noncancer- related conditions is allowed
* Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade = 1 or baseline
* Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation, radiation to the chest, or to more than 30% of the bone marrow within 4 weeks before the first dose of study intervention
* Participants with prior exposure to immunosuppressive medication within 14 days prior to first study dose
* Participants with a known hypersensitivity to study intervention or any of the excipients of the product or other monoclonal antibodies

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/02/2026
Actual
Sample size
Target
Accrual to date
Final
506
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Auchenflower
Recruitment hospital [3] 0 0
Research Site - Clayton
Recruitment hospital [4] 0 0
Research Site - Heidelberg
Recruitment hospital [5] 0 0
Research Site - St Leonards
Recruitment hospital [6] 0 0
Research Site - Subiaco
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
4066 - Auchenflower
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
2065 - St Leonards
Recruitment postcode(s) [6] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
Belgium
State/province [3] 0 0
Anderlecht
Country [4] 0 0
Belgium
State/province [4] 0 0
Bruges
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Belgium
State/province [6] 0 0
Liège
Country [7] 0 0
Canada
State/province [7] 0 0
British Columbia
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Denmark
State/province [9] 0 0
Copenhagen
Country [10] 0 0
Denmark
State/province [10] 0 0
Herlev
Country [11] 0 0
Denmark
State/province [11] 0 0
Odense C
Country [12] 0 0
Finland
State/province [12] 0 0
Helsinki
Country [13] 0 0
Finland
State/province [13] 0 0
Tampere
Country [14] 0 0
Finland
State/province [14] 0 0
Turku
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Dresden
Country [17] 0 0
Germany
State/province [17] 0 0
Erlangen
Country [18] 0 0
Germany
State/province [18] 0 0
Essen
Country [19] 0 0
Germany
State/province [19] 0 0
Frankfurt
Country [20] 0 0
Germany
State/province [20] 0 0
Hamburg
Country [21] 0 0
Germany
State/province [21] 0 0
Hannover
Country [22] 0 0
Germany
State/province [22] 0 0
Kiel
Country [23] 0 0
Germany
State/province [23] 0 0
Mannheim
Country [24] 0 0
Germany
State/province [24] 0 0
München
Country [25] 0 0
Germany
State/province [25] 0 0
Münster
Country [26] 0 0
Germany
State/province [26] 0 0
Tübingen
Country [27] 0 0
Ireland
State/province [27] 0 0
Cork
Country [28] 0 0
Ireland
State/province [28] 0 0
Dublin
Country [29] 0 0
Italy
State/province [29] 0 0
Ancona
Country [30] 0 0
Italy
State/province [30] 0 0
Bergamo
Country [31] 0 0
Italy
State/province [31] 0 0
Catania
Country [32] 0 0
Italy
State/province [32] 0 0
Milano
Country [33] 0 0
Italy
State/province [33] 0 0
Napoli
Country [34] 0 0
Italy
State/province [34] 0 0
Padova
Country [35] 0 0
Italy
State/province [35] 0 0
Prato
Country [36] 0 0
Japan
State/province [36] 0 0
Isehara
Country [37] 0 0
Japan
State/province [37] 0 0
Kawasaki-shi
Country [38] 0 0
Japan
State/province [38] 0 0
Sapporo-shi
Country [39] 0 0
Japan
State/province [39] 0 0
Shinagawa-ku
Country [40] 0 0
Japan
State/province [40] 0 0
Yokohama-shi
Country [41] 0 0
Netherlands
State/province [41] 0 0
Den Haag
Country [42] 0 0
Netherlands
State/province [42] 0 0
Maastricht
Country [43] 0 0
Norway
State/province [43] 0 0
Bergen
Country [44] 0 0
Norway
State/province [44] 0 0
Oslo
Country [45] 0 0
Poland
State/province [45] 0 0
Gdansk
Country [46] 0 0
Poland
State/province [46] 0 0
Kraków
Country [47] 0 0
Poland
State/province [47] 0 0
Opole
Country [48] 0 0
Poland
State/province [48] 0 0
Warszawa
Country [49] 0 0
Portugal
State/province [49] 0 0
Lisboa
Country [50] 0 0
Portugal
State/province [50] 0 0
Porto
Country [51] 0 0
Spain
State/province [51] 0 0
Barcelona
Country [52] 0 0
Spain
State/province [52] 0 0
Bilbao (Vizcaya)
Country [53] 0 0
Spain
State/province [53] 0 0
Granada
Country [54] 0 0
Spain
State/province [54] 0 0
Madrid
Country [55] 0 0
Spain
State/province [55] 0 0
Salamanca
Country [56] 0 0
Spain
State/province [56] 0 0
Santander
Country [57] 0 0
Spain
State/province [57] 0 0
Santiago De Compostela-Coruña
Country [58] 0 0
Spain
State/province [58] 0 0
Sevilla
Country [59] 0 0
Spain
State/province [59] 0 0
Valencia
Country [60] 0 0
Sweden
State/province [60] 0 0
Göteborg
Country [61] 0 0
Sweden
State/province [61] 0 0
Lund
Country [62] 0 0
Sweden
State/province [62] 0 0
Uppsala
Country [63] 0 0
Switzerland
State/province [63] 0 0
Basel
Country [64] 0 0
Switzerland
State/province [64] 0 0
Bellinzona
Country [65] 0 0
Switzerland
State/province [65] 0 0
Lausanne
Country [66] 0 0
Switzerland
State/province [66] 0 0
Luzern
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Edinburgh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Daiichi Sankyo
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nadia Harbeck, MD, PhD
Address 0 0
Head, Breast Center, Ludwig-Maximilians-University of Munich Department of Obstetrics and Gynecology Marchioninistr. 15, 81377 Munich, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04739761