NCT05710666

Neoadjuvant Trastuzumab Deruxtecan (T-DXd) With Response-directed Definitive Therapy in Early Stage HER2-positive Breast Cancer (SHAMROCK Study)

Single Arm Phase 2 Trial of Neoadjuvant Trastuzumab Deruxtecan (T-DXd) With Response-directed Definitive Therapy in Early Stage HER2-positive Breast Cancer: a Standard Chemotherapy-sparing Approach to Curative-intent Treatment - SHAMROCK Study

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: Cancer Trials Ireland · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is a Phase 2 open label, single arm, adaptive multi-centre trial. Patients with early stage HER2-positive breast cancer will receive neoadjuvant treatment of trastuzumab deruxtecan (T-DXd) 5.4mg/kg intravenously every three weeks for up to six cycles.

Detailed description

In this single arm Phase 2 trial we will administer T-DXd 5.4mg/kg intravenously every three weeks for up to six cycles. A mandatory repeat biopsy at Cycle 2 Day 14 +/- 4 days of starting T-DXd will be performed for the RNA Disruption Index (RDI) score assessment. As a safety measure patients will undergo clinical examination before each cycle of T-DXd to enable early identification of on-treatment locoregional progression. If progression is seen then T-DXd will be stopped and the patient will be taken off study treatment. In the absence of early progression, those patients with a high chance of pathological complete response (pCR) based on the RDI score will undergo repeat breast imaging after four cycles of T-DXd. Patients who have a high chance of pCR based on the RDI score will proceed to surgery after four cycles of T-DXd if they also have imaging complete response (iCR) at that point. Other patients who have a high chance of pCR based on the RDI score but iCR is not attained after four cycles or who have a low/intermediate chance of pCR based on the RDI score will undergo repeat breast imaging after six cycles of T-DXd. Patients with iCR after six cycles of T-DXd regardless of RDI score will proceed to surgery. Patients who have a low/intermediate chance of pCR based on the RDI score and residual disease on imaging after six cycles of T-DXd will undergo either further systemic therapy or proceed to surgery (at the discretion of their treating physician). Based on the surgical specimen, patients who achieve a pCR will undergo further trastuzumab post-operatively to complete a total of 52 weeks of systemic therapy from the first cycle of T-DXd. Patients with residual disease at surgery will receive adjuvant chemotherapy as decided by the treating physician.

Conditions

• HER2-positive Breast Cancer

Interventions

Type	Name	Description
DRUG	trastuzumab deruxtecan (T-DXd) (IV)	Administered as an intravenous (IV) infusion at a dose of 5.4 mg/kg on Day 1 of each 21-day cycle for up to six cycles.

Timeline

• Start date: 2023-10-26
• Primary completion: 2025-09-30
• Completion: 2028-03-30
• First posted: 2023-02-02
• Last updated: 2024-08-05

Locations

5 sites across 1 country: Ireland