NCT07421141

De-escalation of Neoadjuvant Treatment (Paclitaxel + HP) in Early HER2+ Breast Cancer

Prospective Non-Randomized Phase II Study of De-escalated Neoadjuvant Chemotherapy With Paclitaxel, Trastuzumab, and Pertuzumab (THP) Compared to Standard Regimen (TCHP) in Patients With Early HER2-Positive Breast Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 186 (actual)
• Sponsor: National Medical Research Radiological Centre of the Ministry of Health of Russia · Academic / Other
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This phase II study evaluates the efficacy and safety of a de-escalated neoadjuvant chemotherapy regimen in patients with early-stage HER2-positive breast cancer. The experimental regimen consists of 12 weekly cycles of paclitaxel combined with trastuzumab and pertuzumab (THP), without anthracyclines. The study aims to determine if this less toxic regimen can achieve high rates of pathological complete response (pCR) comparable to standard anthracycline-containing regimens. The results are compared with a historical control group of patients who received the standard TCHP regimen (docetaxel, carboplatin, trastuzumab, pertuzumab). A total of 186 participants are included in the analysis: 93 patients prospectively treated with the de-escalated THP regimen and 93 patients in the retrospective historical control group (TCHP). The primary endpoint is the pCR rate at the time of surgery. Secondary endpoints include toxicity, rate of breast-conserving surgery, and 3-year event-free survival.

Detailed description

Background: Standard neoadjuvant therapy for HER2-positive breast cancer often includes anthracyclines (AC-THP) or platinum-based regimens (TCHP), which are associated with significant toxicity. De-escalation strategies aim to reduce toxicity without compromising efficacy, particularly in patients with early-stage disease. Study Design: This is an investigator-initiated, single-center, open-label, non-randomized phase II study. * Prospective Cohort (n=93): Patients with Stage IIA-IIB (cT1-2 N0-1, cT3 N0) HER2+ breast cancer receive Paclitaxel (80 mg/m2 weekly for 12 weeks) + Trastuzumab (loading 8 mg/kg, then 6 mg/kg q3w) + Pertuzumab (loading 840 mg, then 420 mg q3w). * Historical Control Cohort (n=93): Patients with similar baseline characteristics (Stage IIA-IIB) treated with standard TCHP regimen (Docetaxel 75 mg/m2 + Carboplatin AUC6 + Trastuzumab + Pertuzumab q3w for 6 cycles). Primary Objective: To evaluate the pathological complete response (pCR, ypT0/is ypN0) rate in the de-escalated arm. Secondary Objectives: 1. To compare the safety profile (incidence of Grade 3-4 adverse events) between THP and TCHP regimens. 2. To assess the rate of breast-conserving surgery. 3. To evaluate long-term oncological outcomes (3-year Event-Free Survival). The study hypothesis is that the de-escalated THP regimen provides a favorable toxicity profile while maintaining high efficacy in a selected population of early HER2+ breast cancer patients.

Conditions

• Breast Cancer
• HER2-positive Breast Cancer
• Early Breast Cancer

Interventions

Type	Name	Description
DRUG	Paclitaxel	80 mg/m2 IV weekly for 12 weeks
DRUG	trastuzumab	Loading dose 8 mg/kg, then 6 mg/kg IV every 3 weeks
DRUG	Pertuzumab	Loading dose 840 mg, then 420 mg IV every 3 weeks
DRUG	Docetaxel	75 mg/m2 IV every 3 weeks for 6 cycles
DRUG	carboplatin	AUC 6 IV every 3 weeks for 6 cycles
PROCEDURE	Radical Surgery	Standard radical resection (mastectomy or breast-conserving surgery) with axillary staging (sentinel lymph node biopsy and/or axillary lymph node dissection \[Levels I-II\], according to current clinical guidelines).
DRUG	Adjuvant Systemic Therapy	Risk-adapted post-neoadjuvant treatment based on pathological response: * Patients with pCR (ypT≤1a, ypN0, RCB 0-I) receive Trastuzumab to complete 1 year of anti-HER2 therapy (combined with endocrine therapy for luminal subtypes). * Patients with residual disease (ypT≥1b and/or ypN+ and/or RCB II-III) receive Trastuzumab emtansine (T-DM1) 3.6 mg/kg every 3 weeks for up to 14 cycles (combined with endocrine therapy for luminal subtypes). Adjuvant radiotherapy is administered if clinically indicated.

Timeline

• Start date: 2023-09-01
• Primary completion: 2025-12-10
• Completion: 2028-12-30
• First posted: 2026-02-19
• Last updated: 2026-02-27

Locations

1 site across 1 country: Russia