A study to investigate the efficacy and safety of trastuzumab deruxtecan in patients With or Without Brain Metastasis Who Have Previously-Treated Advanced or Metastatic HER2 Positive Breast Cancer
- Conditions
- Treatment of patients with HER2-positive breast cancer with or without brain metastasisMedDRA version: 23.0Level: PTClassification code 10065430Term: HER2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-005048-46-IT
- Lead Sponsor
- ASTRAZENECA AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 500
Key inclusion Criteria:
1. Pathologically documented breast cancer that:
(a) Is unresectable/advanced or metastatic, and
(b) Has confirmed HER2+ expression
2. Participant must have either:
(a) No evidence of BM, or
(b) Untreated BM not needing immediate local therapy, or
- For participants with untreated CNS lesions > 2.0 cm on screening contrast brain MRI, discussion with and approval from the study physician is required prior to enrollment, or
(c) Previously treated stable or progressing BM
- Previously treated BM with local therapy may either be radiographically stable for >= 4 weeks since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy
- Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during screening for this study who also have other sites of disease assessable by RECIST 1.1
3. Participants with brain metastases must be neurologically stable and:
(a) Be receiving the equivalent of dexamethasone <= 2 mg/day
(b) If receiving an anticonvulsant regimen, the regimen must have been stable for >= 14 days
(c) Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
4. Radiologic or objective evidence of disease progression on trastuzumab, pertuzumab, or T-DM1 (<= 2 lines/regimens of therapy in the metastatic setting)
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
1. Known or suspected LMD
2. Prior exposure to tucatinib treatment
3. Based on screening brain MRI, 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 brain metastases at a total daily dose of > 2 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 brain metastases notwithstanding CNS-directed therapy
4. Has spinal cord compression
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To describe the overall treatment effect of T-DXd in HER2+ MBC patients with or without baseline brain metastasis;Secondary Objective: 1. To describe the treatment effect on the development and progression of brain metastasis in patients with or without baseline brain metastasis using additional efficacy measurements<br>2. To describe efficacy in patients with stable or untreated brain metastasis<br>3. To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC patients with or without baseline brain metastasis<br>4. To describe the safety profile of T-DXd;Primary end point(s): Participants without BM at baseline (Cohort 1):<br>- ORR by RECIST 1.1<br>Participants with BM at baseline (Cohort 2):<br>- PFS by RECIST 1.1;Timepoint(s) of evaluation of this end point: Assessed until progression or death
- Secondary Outcome Measures
Name Time Method