NCT05323955

Secondary BRain Metastases Prevention After Isolated Intracranial Progression on Trastuzumab/Pertuzumab or T-DM1 in Patients With aDvanced Human Epidermal Growth Factor Receptor 2+ brEast Cancer With the Addition of Tucatinib

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: Carey Anders, M.D. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Patients with advanced HER2+ breast cancer on maintenance trastuzumab/pertuzumab or T-DM1 with 1st or 2nd intracranial disease event (brain metastases) and stable extracranial disease will be enrolled. They will receive local therapy with stereotactic radiosurgery ± surgical resection if indicated followed by enrollment. Patients will continue standard of care trastuzumab/pertuzumab or T-DM1 with the addition of tucatinib. Hormone receptor positive patients requiring endocrine therapy should continue. Study treatment will continue until disease progression or intolerable side effects. Patients on trial with extracranial disease progression with stable intracranial disease should continue tucatinib into next line of therapy.

Detailed description

Patients with advanced HER2+ breast cancer on either (1) first-line trastuzumab/pertuzumab OR (2) second-line T-DM1 in the metastatic setting OR (3) adjuvant trastuzumab-based therapy or T-DM1 with isolated intracranial recurrence will be included. Patients with de novo metastatic disease and brain metastases or isolated intracranial recurrence can enter upon initiation of maintenance trastuzumab/pertuzumab after chemotherapy if deemed necessary by treating oncologist and meeting other inclusion criteria. Patients with 1st or 2nd intracranial disease event (brain metastases) and stable extracranial disease will be enrolled. Third intracranial progression would be considered if \> 12 month interval between second and third intracranial progression. They will receive local therapy with stereotactic radiosurgery ± surgical resection followed by enrollment. Patients will continue standard of care treatment trastuzumab/pertuzumab or T-DM1 with the addition of tucatinib. Hormone receptor-positive patients requiring endocrine therapy should continue. Study treatment will continue until intercranial disease progression or intolerable side effects. Patients with extracranial disease progression while on trial with stable intracranial disease should continue tucatinib into the next line of therapy as described in protocol. If a subject continues tucatinib into the next line therapy they are still considered on study treatment and will be monitored according to the protocol. Cycles will continue consecutively and not restart. Once the subject comes off tucatinib they are considered off study treatment and will enter the follow up period.

Conditions

• Brain Metastases
• Human Epidermal Growth Factor 2 Positive Carcinoma of Breast
• Advanced Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab	Administer per current package insert based on site standard of care guidelines
DRUG	Trastuzumab Emtansine (T-DM1)	Administer per current package insert based on site standard of care guidelines
DRUG	Pertuzumab	Administer per current package insert based on site standard of care guidelines
DRUG	Tucatinib	300 mg orally twice daily (21 Day Cycle)

Timeline

• Start date: 2023-03-23
• Primary completion: 2026-04-01
• Completion: 2026-07-01
• First posted: 2022-04-12
• Last updated: 2026-03-17

Locations

8 sites across 1 country: United States

Regulatory

• FDA-regulated drug study