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

NCT07421141 | Active Not Recruiting Phase 2

• 2 other identifiers: Opti-HER2-2023LEC #962/107
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer; HER2-positive Breast Cancer; Early Breast Cancer

Keywords

Neoadjuvant Therapy; De-escalation; Paclitaxel; Trastuzumab; Pertuzumab; Pathological Complete Response; THP Regimen

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  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 Outcomes (3)

• Incidence of Grade 3-4 Adverse Events

  From first dose until 30 days after last dose

• Rate of Breast-Conserving Surgery

  At the time of surgery

• 3-Year Event-Free Survival (EFS)

  3 years from enrollment

Study Arms (2)

Experimental: De-escalated THP

EXPERIMENTAL

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; Drug: trastuzumab; Drug: Pertuzumab; Procedure: Radical Surgery; Drug: Adjuvant Systemic Therapy

Historical Control: Standard TCHP

ACTIVE COMPARATOR

Retrospective cohort of patients who received standard neoadjuvant chemotherapy with Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP regimen) for 6 cycles.

Drug: trastuzumab; Drug: Pertuzumab; Drug: Docetaxel; Drug: carboplatin; Procedure: Radical Surgery; Drug: Adjuvant Systemic Therapy

Interventions

Paclitaxel DRUG

80 mg/m2 IV weekly for 12 weeks

Also known as: Taxol

Experimental: De-escalated THP

trastuzumab DRUG

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

Also known as: Herceptin

Experimental: De-escalated THP; Historical Control: Standard TCHP

Pertuzumab DRUG

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

Also known as: Perjeta

Experimental: De-escalated THP; Historical Control: Standard TCHP

Docetaxel DRUG

75 mg/m2 IV every 3 weeks for 6 cycles

Also known as: Taxotere

Historical Control: Standard TCHP

carboplatin DRUG

AUC 6 IV every 3 weeks for 6 cycles

Also known as: Paraplatin

Historical Control: Standard TCHP

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).

Experimental: De-escalated THP; Historical Control: Standard TCHP

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.

Also known as: Trastuzumab, T-DM1, Trastuzumab Emtansine

Experimental: De-escalated THP; Historical Control: Standard TCHP

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Medical Research Radiological Centre of the Ministry of Health of Russia: lead

Study Sites (1)

P.A. Hertsen Moscow Oncology Research Institute

Moscow, 125284, Russia

Location

Related Publications (3)

• Nitz UA, Gluz O, Christgen M, Grischke EM, Augustin D, Kuemmel S, Braun M, Potenberg J, Kohls A, Krauss K, Stefek A, Schumacher C, Forstbauer H, Reimer T, Fischer H, Liedtke C, Wuerstlein R, Schumacher J, Kates R, Kreipe H, Harbeck N. De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab +/- weekly paclitaxel. Ann Oncol. 2017 Nov 1;28(11):2768-2772. doi: 10.1093/annonc/mdx494.

  PMID: 28945833 BACKGROUND

• Waks AG, Desai NV, Li T, Poorvu PD, Partridge AH, Sinclair N, Spring LM, Faggen M, Constantine M, Metzger O, Alberti J, Deane J, Rosenberg SM, Frank E, Tolaney SM, Krop IE, Tung NM, Tayob N, King TA, Mittendorf EA, Winer EP. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022 May 10;8(1):63. doi: 10.1038/s41523-022-00429-7.

  PMID: 35538105 BACKGROUND

• Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortes J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. doi: 10.1093/annonc/mdt182. Epub 2013 May 22.

  PMID: 23704196 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Trastuzumab; pertuzumab; Docetaxel; Carboplatin; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Maytansine; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Larisa Bolotina, MD, PhD

  P.A. Hertsen Moscow Oncology Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective single-arm de-escalation cohort compared with a retrospective historical control cohort.

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 19, 2026
• Study Start: September 1, 2023
• Primary Completion: December 10, 2025
• Study Completion (Estimated): December 30, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)