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Phase II Study of T-DX in HER2-positive Breast Cancer Brain Metastases (TUXEDO-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04752059
Recruitment Status : Completed
First Posted : February 12, 2021
Last Update Posted : May 12, 2023
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):
Rupert Bartsch, Medical University of Vienna

Brief Summary:
Trastuzumab-Deruxtecan (T-DXd; DS-8201a) in HER2-positive Breast Cancer Patients with newly diagnosed or progressing Brain Metastases

Condition or disease Intervention/treatment Phase
Breast Cancer Stage IV Drug: Trastuzumab deruxtecan Phase 2

Detailed Description:
T-DXd will be administered at a dose of 5.4 mg/kg body weight once every three weeks in patients with newly diagnosed or progressive HER2 positive breast cancer brain metastases. Response rate by RANO-BM is defined the primary study endpoint.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Trastuzumab-Deruxtecan (T-DX; DS-8201a) in HER2-positive Breast Cancer Patients With Newly Diagnosed or Progressing Brain Metastases
Actual Study Start Date : July 28, 2020
Actual Primary Completion Date : May 1, 2023
Actual Study Completion Date : May 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: T-DXd 5.4 mg
Single arm phase II trial
Drug: Trastuzumab deruxtecan
Trastuzumab-deruxtecan 5.4 mg/kg body weight i.v. on day 1 once every three weeks until progression or death
Other Names:
  • Ds8201a
  • Enhertu

Primary Outcome Measures :
  1. Reponse rate of brain metastases to trastuzumab-deruxtecan [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed up to 36 months ]
    measured according to RANO-BM criteria

Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed up to 36 months ]
    Time from inclusion until progression

  2. Overall Survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed up to 36 months ]
    Time from inclusion until death of any cause

  3. Safety of trastuzumab deruxtecan in patients with active brain metastases [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed up to 36 months ]
    Assessment of treatment-emerging adverse events

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Histologically confirmed breast cancer

  • Radiologically documented metastatic disease
  • HER2-positive as defined by IHC 3+ and/or HER2/neu gene amplification
  • Newly diagnosed brain metastases or brain metastases progressing after prior local therapy
  • Measurable disease (RANO-BM criteria)
  • No indication for immediate local treatment
  • No indication of leptomeningeal disease
  • KPS >70%, ECOG <2
  • Indication for systemic anti-HER2 treatment
  • Prior exposure to trastuzumab and pertuzumab
  • Prior exposure to T-DM1 allowed
  • Life expectancy of at least 3 months
  • Age ≥18 years
  • Patient must be able to tolerate therapy, and have adequate cardiac function (defined by baseline left ventricular ejection fraction ≥50%) Adequate bone-marrow, liver and kidney function
  • Adequate treatment washout period before enrolment, defined as:
  • Major Surgery: ≥4 weeks
  • Radiation therapy: ≥4 weeks
  • Chemotherapy, small-molecule targeted agents, anticancer hormonal therapy: ≥3 weeks
  • Antibody-based treatment: ≥4 weeks
  • Patient must be capable of understanding the purpose of the study and have given written informed consent

Exclusion Criteria:

Metastatic breast cancer other than HER2-positve disease

  • Use of any investigational agent within 28 days prior to initiation of treatment
  • History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 3 years including contralateral breast cancer
  • Major surgery, other than diagnostic surgery, within the last 4 weeks
  • Indication for immediate local therapy as defined by local standard
  • Leptomeningeal involvement
  • Other anticancer therapy, including cytotoxic, targeted agents, immunotherapy, antibody, retinoid, or anti-cancer hormonal treatment
  • Concomitant radiotherapy
  • Prior radiotherapy to the thorax other than breast irradiation or irradiation of bone metastases
  • A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), left ventricular ejection fraction <50%, arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities, and long QT syndrome (QTc interval >450 ms)
  • Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) including acute and chronic infections with hepatitis B and C
  • Inadequate haematological status at baseline prior to study entry: Dependency on red blood cell and/or platelet transfusions, ANC (absolute neutrophil count (segmented + bands) <1.0 x 109/L; platelets <100 x 109/L
  • Inadequate kidney function: serum-creatinine >1.5 times upper normal Limit Hepatic dysfunction: total bilirubin >1.5 times upper normal limit (>3 in patients with liver metastases or known history of Gilbert's disease); ALT, AST >3 times TUXEDO-1_Version 2.0 05.05.2020 Page 8 of 73 upper normal limit (>5 in patients with liver metastases); serum albumin <2.5 g/dL; INR ≥1.5
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrolment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (i.e. rheumatoid arthritis, Sjogren's syndrome, sarcoidosis etc.), or prior pneumonectomy.

Subjects with bronchopulmonary disorders who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study

  • Patients with active opportunistic infections
  • Known HIV infection
  • Concomitant treatment with chloroquine or hydroxychloroquine
  • Pregnant or lactating women. Women with childbearing potential must have a negative pregnancy test at screening
  • Women with childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Acceptable contraception methods included the application of an intrauterine device, barrier method or total abstinence
  • Patients with known hypersensitivity to trastuzumab
  • Patients not able to provide written informed consent Patients with known substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
  • Patients requiring concomitant use of chronic systemic (IV or oral) corticosteroids at doses higher than 4 mg dexamethasone per day or other immunosuppressive medications except for managing adverse events (inhaled steroids or intra articular steroid injections are permitted in this study)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04752059

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AKH Universitaetsklinikum Vienna, Department f. Internal medicine I, oncology
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Daiichi Sankyo, Inc.
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Principal Investigator: Rupert Bartsch, MD Medical University of Vienna
  Study Documents (Full-Text)

Documents provided by Rupert Bartsch, Medical University of Vienna:
Publications of Results:
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Responsible Party: Rupert Bartsch, Consultant Medical Oncology, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT04752059    
Other Study ID Numbers: TUXEDO-1
First Posted: February 12, 2021    Key Record Dates
Last Update Posted: May 12, 2023
Last Verified: May 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Brain Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Trastuzumab deruxtecan
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs