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

Medical University of Vienna

Status and phase

Completed

Phase 2

Conditions

Breast Cancer Stage IV

Treatments

Drug: Trastuzumab deruxtecan

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04752059

TUXEDO-1

Details and patient eligibility

About

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

Full 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.

Enrollment

15 patients

Sex

Female

Ages

18 to 100 years old

Volunteers

No Healthy Volunteers

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)