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

February 24, 2026 updated by: National Medical Research Radiological Centre of the Ministry of Health of Russia

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

186

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russia
      • Moscow, Russia, 125284
        • P.A. Hertsen Moscow Oncology Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: De-escalated THP
Patients receive de-escalated neoadjuvant chemotherapy consisting of 12 weekly cycles of Paclitaxel combined with Trastuzumab and Pertuzumab (THP regimen), followed by surgery.
Drug: Paclitaxel
80 mg/m2 IV weekly for 12 weeks
Other Names:
  • Taxol
Drug: trastuzumab
Loading dose 8 mg/kg, then 6 mg/kg IV every 3 weeks
Other Names:
  • Herceptin
Drug: Pertuzumab
Loading dose 840 mg, then 420 mg IV every 3 weeks
Other Names:
  • Perjeta
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.

Other Names:
  • T-DM1
  • Trastuzumab
  • Trastuzumab Emtansine
Active Comparator: Historical Control: Standard TCHP
Retrospective cohort of patients who received standard neoadjuvant chemotherapy with Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP regimen) for 6 cycles.
Drug: trastuzumab
Loading dose 8 mg/kg, then 6 mg/kg IV every 3 weeks
Other Names:
  • Herceptin
Drug: Pertuzumab
Loading dose 840 mg, then 420 mg IV every 3 weeks
Other Names:
  • Perjeta
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.

Other Names:
  • T-DM1
  • Trastuzumab
  • Trastuzumab Emtansine
Drug: Docetaxel
75 mg/m2 IV every 3 weeks for 6 cycles
Other Names:
  • Taxotere
Drug: carboplatin
AUC 6 IV every 3 weeks for 6 cycles
Other Names:
  • Paraplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
At the time of surgery (approximately 12-18 weeks after treatment initiation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Breast-Conserving Surgery
Time Frame: At the time of surgery
Proportion of patients eligible for and undergoing breast-conserving surgery
At the time of surgery
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
3 years from enrollment
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.
From first dose until 30 days after last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Investigators

  • Principal Investigator: Larisa Bolotina, MD, PhD, P.A. Hertsen Moscow Oncology Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2023

Primary Completion (Actual)

December 10, 2025

Study Completion (Estimated)

December 30, 2028

Study Registration Dates

First Submitted

February 9, 2026

First Submitted That Met QC Criteria

February 12, 2026

First Posted (Actual)

February 19, 2026

Study Record Updates

Last Update Posted (Actual)

February 27, 2026

Last Update Submitted That Met QC Criteria

February 24, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Opti-HER2-2023
  • LEC #962/107 (Other Identifier: Ethics Council, P.A. Hertsen MORI)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared due to patient confidentiality requirements

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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