Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT07421141

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Early Breast Cancer HER2-positive Breast Cancer Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year–75 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

P.A. Hertsen Moscow Oncology Research Institute

Moscow, 125284, Russia

About this study

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:

  • To compare the safety profile (incidence of Grade 3-4 adverse events) between THP and TCHP regimens.
  • To assess the rate of breast-conserving surgery.
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically confirmed invasive breast carcinoma.
  • HER2-positive status defined as IHC 3+ or FISH amplification (ratio >= 2.0).
  • Clinical Stage IIA-IIB (cT1-T2 N0-N1, cT3 N0, M0).
  • Operable disease planned for surgical resection.
  • ECOG performance status 0-1.
  • Left Ventricular Ejection Fraction (LVEF) >= 50% by Echocardiography.
  • Adequate bone marrow, hepatic, and renal function.
  • Signed informed consent form.

Exclusion criteria

  • Metastatic disease (Stage IV).
  • Prior systemic therapy for breast cancer (chemotherapy, immunotherapy, or anti-HER2 therapy).
  • Serious cardiac history (congestive heart failure, unstable angina, myocardial infarction within 6 months).
  • Other synchronous or metachronous malignancies within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix).
  • Pregnancy or breastfeeding.
  • Known hypersensitivity to study drugs.

Treatment and study plan

paclitaxel

Drug

80 mg/m2 IV weekly for 12 weeks

Other names: Taxol

Trastuzumab

Drug

Loading dose 8 mg/kg, then 6 mg/kg IV every 3 weeks

Other names: Herceptin

Pertuzumab

Drug

Loading dose 840 mg, then 420 mg IV every 3 weeks

Other names: Perjeta

docetaxel

Drug

75 mg/m2 IV every 3 weeks for 6 cycles

Other names: Taxotere

carboplatin

Drug

AUC 6 IV every 3 weeks for 6 cycles

Other names: Paraplatin

Radical surgery

Procedure

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).

Adjuvant Systemic Therapy

Drug

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.

Other names: Trastuzumab, T-DM1, Trastuzumab Emtansine

Primary outcomes

  1. Pathological Complete Response (pCR) Rate

    Time frame: At the time of surgery (approximately 12-18 weeks after treatment initiation)

    Defined as the absence of invasive cancer in the breast and axillary lymph nodes (ypT0/is ypN0) at the time of surgery

Secondary outcomes

  1. Incidence of Grade 3-4 Adverse Events

    Time frame: From first dose until 30 days after last dose

    Assessment of treatment-related toxicity (neutropenia, diarrhea, etc.) according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0, where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death.

  2. Rate of Breast-Conserving Surgery

    Time frame: At the time of surgery

    Proportion of patients eligible for and undergoing breast-conserving surgery

  3. 3-Year Event-Free Survival (EFS)

    Time frame: 3 years from enrollment

    Time from enrollment to disease progression, local recurrence, distant metastasis, or death from any cause

Sponsors and collaborators

Lead sponsor

National Medical Research Radiological Centre of the Ministry of Health of Russia

Other

Registry information

Official study title

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

Acronym: Opti-HER2

Important dates

Study start
2023
Primary completion
2025
Study completion
2028
First posted
Feb 19, 2026
Registry last updated
Feb 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.