Phase II Study of T-DX in HER2-positive Breast Cancer Brain Metastases

NCT04752059 | Completed Phase 2

• 1 other identifier: TUXEDO-1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Breast Cancer Stage IV

Outcome Measures

Primary Outcomes (1)

• Reponse rate of brain metastases to trastuzumab-deruxtecan

  measured according to RANO-BM criteria

  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

Secondary Outcomes (3)

• Progression-free survival

  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

• Overall Survival

  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

• Safety of trastuzumab deruxtecan in patients with active brain metastases

  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

Study Arms (1)

T-DXd 5.4 mg

EXPERIMENTAL

Single arm phase II trial

Drug: Trastuzumab deruxtecan

Interventions

Trastuzumab deruxtecan DRUG

Trastuzumab-deruxtecan 5.4 mg/kg body weight i.v. on day 1 once every three weeks until progression or death

Also known as: Ds8201a, Enhertu

T-DXd 5.4 mg

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead
• Daiichi Sankyo: collaborator

Study Sites (1)

AKH Universitaetsklinikum Vienna, Department f. Internal medicine I, oncology

Vienna, 1090, Austria

Location

Related Publications (1)

• Bartsch R, Berghoff AS, Furtner J, Marhold M, Bergen ES, Roider-Schur S, Starzer AM, Forstner H, Rottenmanner B, Dieckmann K, Bago-Horvath Z, Haslacher H, Widhalm G, Ilhan-Mutlu A, Minichsdorfer C, Fuereder T, Szekeres T, Oehler L, Gruenberger B, Singer CF, Weltermann A, Puhr R, Preusser M. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nat Med. 2022 Sep;28(9):1840-1847. doi: 10.1038/s41591-022-01935-8. Epub 2022 Aug 8.

  PMID: 35941372 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Rupert Bartsch, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Medical Oncology

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: February 12, 2021
• Study Start: July 28, 2020
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: May 12, 2023

Record last verified: 2023-05

Locations

AU (1)