HER2-positive Breast Cancer with newly diagnosed or progressing Brain Metastases
Conditions
Interventions
Product Name: Trastuzumab-Deruxtecan
Product Code: T-DXd
DS-8201a
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: TRASTUZUMAB DERUXTECAN
CAS Number: 1826843-81-5
Current Sponsor code: Tuxedo1
Concentration unit: mg milligram(s)
Co
Sponsors
Med. Univ. Wien, Klinik f. Innere Mdizin I, Onkologie
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
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 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 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) 1.5 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 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 potential 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 • 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 • Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy • Pat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the ability of trastuzumab-deruxtecan to induce CNS responses in patients with HER2-positive breast cancer and newly diagnosed multiple brain metastases.;Secondary Objective: To evaluate the activity of trastuzumab-deruxtecan on extracranial disease, safety and tolerability of trastuzumab-deruxtecan in the patient population and QoL of study subjects. Exploratory Objectives: To evaluate biomarkers associated with response to trastuzumab-deruxtecan. ;Primary end point(s): The primary endpoint of this study is the rate of best responses of BM at any assessment after the administration of at least one cycle of the IMP defined as CR, PR, SD and PD according to the RANO criteria and as determined by the local investigator.;Timepoint(s) of evaluation of this end point: After 3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study consist of Clinical Benefit Rate CNS (CBR CNS; CR+PR+SD =6 months), extracranial response rate defines as CR, PR, SD and PD according to RECIST 1.1 criteria, progression-free survival defined as the interval from study inclusion until progression or death, time-to-WBRT defined as the interval from study inclusion until WBRT, overall survival defined as the interval from study inclusion until death, safety and QoL. Exploratory Endpoints: Exploratory endpoints of this study include the number of HER/neu gene copies and the rate of TILs. For ancillary biomarker studies, blood samples (3 ml EDTA, 3 ml serum) will be drawn before administration of the IMP at cycles 1 and 4 and at EOT. ;Timepoint(s) of evaluation of this end point: After 3 years | — |
Countries
Austria
Contacts
Public ContactRupert Bartsch
Med. Univ. Wien, Klinik f. Innere Mdizin I, Onkologie
Outcome results
None listed