NCT05041842

Treatment With Tucatinib in Patients With an Isolated Brain Progression of a Metastatic Breast Cancer

Treatment With Tucatinib in Addition to Pertuzumab and Trastuzumab in Patients With HER2-positive Metastatic Breast Cancer After Local Therapy of Isolated Brain Progression

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 53 (actual)
• Sponsor: UNICANCER · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The overall survival of patients with metastatic breast cancer has steadily improved over the past decades, mainly due to advances in systemic treatment. Despite these advances, the development of brain metastases remains a serious and devastating complication that decreases quality of life and increases morbidity and mortality. The HER2CLIMB randomized study demonstrated that adding the investigational drug tucatinib to the standard treatment trastuzumab and capecitabine improved both progression-free survival and overall survival in people diagnosed with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer, previously treated with trastuzumab, pertuzumab, and T-DM1. In patients with brain metastases, the 1-year progression-free survival was 25% in the tucatinib group and 0% in the placebo group. These results suggest that tucatinib may be a new standard treatment for HER2-positive metastatic disease. The aim of the non-randomized phase II study, InTTercePT, is to evaluate the effectiveness of adding tucatinib to trastuzumab and pertuzumab in the event of cerebral progression, after the end of local treatment.

Detailed description

The overall survival of patients with metastatic breast cancer has steadily improved over the past decades, mainly due to advances in systemic treatment. Despite these advances, the development of brain metastases remains a serious and devastating complication that decreases quality of life and increases morbidity and mortality. More than a third of patients with HER2-positive breast cancer develop brain metastases during the course of the disease. For patients with isolated brain progression, local treatment is recommended whenever possible (stereotaxic radiosurgery and / or surgery) as well as the continuation of systemic treatment previously initiated even if the evidence of a benefit is weak. After local treatment these patients will have a higher risk of progression (cerebral and systemic). Therefore, the question of whether systemic treatment should be continued or changed remains an open question. In a pooled analysis of two phase 1b studies, patients who continued systemic treatment with tucatinib (in combination with T-DM1 or with trastuzumab and capecitabine) after treatment directed to the central nervous system demonstrated a better prognosis than that of patients who stopped tucatinib. The HER2CLIMB randomized study demonstrated that adding the investigational drug tucatinib to the standard treatment trastuzumab and capecitabine improved both progression-free survival and overall survival in people diagnosed with HER2-positive metastatic breast cancer, previously treated with trastuzumab, pertuzumab, and T-DM1. In patients with brain metastases, the 1-year progression-free survival was 25% in the tucatinib group and 0% in the placebo group. These results suggest that tucatinib may be a new standard treatment for HER2-positive metastatic disease. We anticipate that adding tucatinib to the trastuzumab / pertuzumab regimen will control brain metastases, prolong progression-free survival, and improve patient quality of life. The aim of the non-randomized phase II study, InTTercePT, is to evaluate the effectiveness of adding tucatinib to trastuzumab and pertuzumab in the event of cerebral progression, after the end of local treatment.

Conditions

• Metastatic Breast Cancer With a Isolated Brain Progression

Interventions

Type	Name	Description
DRUG	Tucatinib	300 mg orally twice daily
DRUG	Pertuzumab	Initial loading: 840 mg Maintenance: 420 mg, 3-weekly
DRUG	Trastuzumab	Intravenous formulation : Initial loading: 8 mg/kg Maintenance: 6 mg/kg, 3-weekly Subcutaneous formulation: 600 mg (fixed dose regardless of patient's body weight), 3-weekly
DRUG	Hormone therapy	Anastrozole (1 mg/day) or letrozole (2.5 mg/day) or fulvestrant (2x250 mg at day 1 and day 15 then every 4 weeks after the first injection)
DRUG	Pertuzumab/ Trastuzumab	Initial loading: 1200 mg Pertuzumab / 600 mg Trastuzumab (regardless of body weight) Maintenance: 600 mg Pertuzumab / 600 mg Trastuzumab (regardless of body weight), 3-weekly

Timeline

• Start date: 2021-12-17
• Primary completion: 2025-04-30
• Completion: 2026-04-30
• First posted: 2021-09-13
• Last updated: 2025-11-17

Locations

16 sites across 1 country: France