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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
2020-005048-46
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 Participants without BM at Baseline (Cohort 1)
Timepoint [1] 0 0
From screening until progression of disease [PD] (Up to 2.5 Years)
Primary outcome [2] 0 0
Progression-free Survival (PFS) in Participants with BM at Baseline (Cohort 2)
Timepoint [2] 0 0
From screening until PD (Up to 2.5 Years)
Secondary outcome [1] 0 0
Overall Survival (OS) in Months
Timepoint [1] 0 0
At safety F/U (40+7 days after last dose) visit, thereafter survival F/U q3months ± 14 days (Approximately 2.5 Years)
Secondary outcome [2] 0 0
Duration of Response (DoR)
Timepoint [2] 0 0
Screening Day (-28 days) until end-of-treatment (EOT) (Approximately 2.5 Years)
Secondary outcome [3] 0 0
Time to Progression
Timepoint [3] 0 0
Screening Day (-28 days) until PD (Approximately 2.5 Years)
Secondary outcome [4] 0 0
Duration of Treatment on Subsequent Lines of Therapy
Timepoint [4] 0 0
At safety follow-up (40+7 days after last dose) then survival F/U q3months ± 14 days (Approximately 2.5 Years)
Secondary outcome [5] 0 0
Time to Second Progression or Death (PFS2)
Timepoint [5] 0 0
At safety F/U (40+7 days after last dose) visit, thereafter survival F/U q3months ± 14 days (Approximately 2.5 Years)
Secondary outcome [6] 0 0
Incidence of new Symptomatic Central Nervous System (CNS) Metastasis During Treatment in Participants without BM at Baseline (Cohort 1)
Timepoint [6] 0 0
At Screening day (-28 days), Cycle 1 (15 days ± 2 days) Day 1 and Cycle 3 (15 days ± 2 days) Day 1 and thereafter every 3 subsequent cycles (Approximately 2.5 Years)
Secondary outcome [7] 0 0
Time to Next Progression (CNS or extracranial) or Death
Timepoint [7] 0 0
Screening Day (-28 days) until next PD (Approximately 2.5 Years)
Secondary outcome [8] 0 0
Site (CNS vs extracranial vs both) of Next Progression
Timepoint [8] 0 0
Screening Day (-28 days) until next PD (Approximately 2.5 Years)
Secondary outcome [9] 0 0
Objective Response Rate in Participants with BM at Baseline (Cohort 2)
Timepoint [9] 0 0
From screening until PD (Up to 2.5 Years)
Secondary outcome [10] 0 0
Central Nervous System Progression-free Survival in Participants with BM at Baseline (Cohort 2)
Timepoint [10] 0 0
At safety follow-up (40+7 days after last dose) then survival F/U q3months ± 14 days (Approximately 2.5 Years)
Secondary outcome [11] 0 0
Time to new CNS Lesions in Participants with BM at Baseline (Cohort 2)
Timepoint [11] 0 0
Screening Day (-28 days) until EOT (Approximately 2.5 Years)
Secondary outcome [12] 0 0
Central Nervous System Objective Response Rate in Participants with BM at Baseline by ICR (Cohort 2)
Timepoint [12] 0 0
Screening Day (-28 days) until EOT (Approximately 2.5 Years)
Secondary outcome [13] 0 0
Central Nervous System Duration of Response in Participants with BM at Baseline (Cohort 2)
Timepoint [13] 0 0
Screening Day (-28 days) until EOT (Approximately 2.5 Years)
Secondary outcome [14] 0 0
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Timepoint [14] 0 0
Cycle 1 (15 days ± 2 days) Day 1, thereafter every 3 weeks (q3w) until 24 weeks post EOT visit and prior to second progression, and at the EOT visit (Approximately 2.5 Years)
Secondary outcome [15] 0 0
Neurologic Assessment in Neuro-Oncology Scale
Timepoint [15] 0 0
Cycle 1 (15 days ± 2 days [Day 1]), Cycle 2 (15 days ± 2 days) Day 1, Cycle 3 (15 days ± 2 days) Day 1, Cycle 4 (15 days ± 2 days) Day 1 thereafter subsequent Cycles until PD and at EOT visit (Approximately 2.5 Years)
Secondary outcome [16] 0 0
Cognitive Functions Tests
Timepoint [16] 0 0
Cycle 1 (15 days ± 2 days) Day 1, thereafter q12w and at EOT visit (Approximately 2.5 Years)
Secondary outcome [17] 0 0
MD Anderson Symptom Inventory Brain Tumor-specific Items
Timepoint [17] 0 0
Cycle 1 (15 days ± 2 days) Day 1, thereafter q3w until 24 weeks post EOT visit and prior to second progression, and at the EOT visit (Approximately 2.5 Years)
Secondary outcome [18] 0 0
St. George's Respiratory Questionnaire - idiopathic pulmonary fibrosis version in Participants with Interstitial Lung Disease (ILD)/Pneumonitis
Timepoint [18] 0 0
After diagnosis of ILD/pneumonitis and thereafter once weekly until EOT and safety F/U (40+7 days after last dose) (Approximately 2.5 Years)
Secondary outcome [19] 0 0
Number of Participants with Adverse Events
Timepoint [19] 0 0
Cycle 1 (15 days ± 2 days) Day 1 until safety F/U (40+7 days after last dose) (Approximately 2.5 Years)
Secondary outcome [20] 0 0
Number of Participants with Investigator-assessed ILD/Pneumonitis or Rate of Investigator-assessed ILD/Pneumonitis
Timepoint [20] 0 0
Cycle 1 (15 days ± 2 days) Day 1 until C4 (15 days ± 2 days) Day 1 and thereafter subsequent cycles until PD (Approximately 2.5 Years)
Secondary outcome [21] 0 0
Number of Participants with Adverse Events with BM at Baseline
Timepoint [21] 0 0
Cycle 1 (15 days ± 2 days) Day 1 until safety F/U (40+7 days after last dose) (Approximately 2.5 Years)

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
NA
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.