Treatment of patients with HER2-positive breast cancer with or without brain metastasis MedDRA version: 23.0 Level: PT Classification code 10065430 Term: HER2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key inclusion Criteria: 1. Pathologically documented breast cancer that: (a) Is unresectable/advanced or metastatic, and (b) Has confirmed HER2-positive status as determined according to ASCO/CAP guidelines (Wolff et al, 2018) evaluated at a local laboratory 2. Participant must have either: (a) No evidence of BM, or (b) Untreated BM on screening contrast brain MRI / CT scan (i)not needing immediate local therapy, or (ii)For participants with untreated CNS lesions: - if lesion = 2 cm, no discussion with study physician is required prior to enrollment - if lesion is > 2.0 cm, discussion with and approval from the study physician is required prior to enrollment, or (c) Previously treated stable or progressing BM (i) Previously treated BM with local therapy may either be radiographically stable for = 4 weeks since completion of treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy (ii) Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI/CT scan performed during screening for this study who also have other sites of disease assessable by RECIST 1.1 3. Participants with BMs must be neurologically stable and: (a) Be receiving the equivalent of dexamethasone = 3 mg/day if treatment is required (b) If receiving an anticonvulsant regimen, the regimen must have been stable for = 14 days before first day of dosing (c) Relevant records of any CNS treatment must be available to allow for classification of TLs and NTLs 4. Previous breast cancer treatment: (a) Radiologic or objective evidence of disease progression on or after HER2 targeted therapies. Note: Disease progression within 6 months after adjuvant treatment with HER2 targeted therapies is also acceptable. (b) No more than 2 lines/regimens of therapy in the metastatic setting. Note: A line/regimen of treatment should be counted based on a progression event. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Known or suspected LMD 2. Prior exposure to tucatinib treatment 3. Based on screening contrast brain MRI/ CT scan, participants must not have any of the following: (a) Any untreated brain lesions > 2.0 cm in size (b) Ongoing use of systemic corticosteroids for control of symptoms of BMs at a total daily dose of > 3 mg of dexamethasone (or equivalent). (c) Any brain lesion thought to require immediate local therapy, (d) Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to BMs notwithstanding CNS-directed therapy 4. Has spinal cord compression
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To describe the overall treatment effect of T DXd in HER2-positive MBC patients with or without baseline BM;Secondary Objective: 1. To describe the treatment effect on the development and progression of BM in patients with or without baseline BM using additional efficacy measurements 2. To describe efficacy in patients with stable or untreated BM 3. To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2-positive MBC patients with or without baseline BM 4. To describe the safety profile of T-DXd;Primary end point(s): Participants without BM at baseline (Cohort 1): ?ORR by RECIST 1.1 per ICR Participants with BM at baseline (Cohort 2): ?PFS by RECIST 1.1 per ICR;Timepoint(s) of evaluation of this end point: - assessed until progression or death | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The timepoints for key secondary endpoints are: please see section secondary endpoints for corresponding timepoints below - assessed until progression or death - AEs and SAEs throughout the treatment period and including the safety follow-up (40+ up to 7 days after discontinuation of all study interventions);Secondary end point(s): 1. Participants in both cohorts: ? - OS ? - DoR by RECIST per ICR ? - Time to progression by RECIST per ICR ? - DoT on subsequent lines of therapy ? - PFS2 Participants without BM at baseline (Cohort 1): ? - Incidence of new symptomatic CNS metastasis during treatment In patients who develop isolated CNS progression, receive local therapy, and continue on protocol therapy: ? - Time to next progression (CNS or extracranial) or death ? - Site (CNS vs extracranial vs both) of next progression 2. Participants with BM at baseline (Cohort 2): ? - ORR by RECIST 1.1 per ICR ? - CNS PFS by CNS RECIST 1.1 per ICR ? - Time to new CNS lesions ? - CNS ORR by CNS RECIST 1.1 per ICR ? - CNS DoR by CNS RECIST 1.1 per ICR 3. Changes in symptoms, functioning, and HRQoL as measured by ? - All patients: EORTC QLQ-C30, NANO scale, cognitive tests ? - BM patients: MDASI brain tumor-specific items ? - ILD/pneumonitis patients: SGRQ-I 4. Safety and tolerability will be evaluated in terms of AEs, vital signs, clinical laboratory results, and ECGs. Assessments related to AEs will also include: ? - Rate of investigator-assessed ILD/pneumonitis ? - Rate of AEs among patients with baseline BM who are treated with concurrent high-dose steroid (total daily dose > 2 mg dexamethasone or equivalent) | — |
Countries
Australia, Belgium, Canada, Denmark, Finland, Germany, Ireland, Italy, Japan, Netherlands, Norway, Poland, Portugal, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed