Pyrotinib Plus Trastuzumab and Chemotherapy for HER2-Positive Early Breast Cancer

Efficacy and Safety of Pyrotinib and Trastuzumab Combined With Pegylated Liposomal Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel for Injection Albumin Bound as Neoadjuvant Therapy for Early HER2-Positive Breast Cancer

This is a single-arm, multicenter clinical study designed to evaluate the efficacy and safety of pyrotinib and trastuzumab combined with pegylated liposomal doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel for injection albumin bound as neoadjuvant therapy in patients with early HER2-positive breast cancer.

Eligible patients will receive 8 cycles of neoadjuvant treatment. Pyrotinib will be administered orally once daily, and trastuzumab will be administered intravenously every 3 weeks. During the first 4 cycles, patients will receive pegylated liposomal doxorubicin hydrochloride and cyclophosphamide. During the subsequent 4 cycles, patients will receive paclitaxel for injection albumin bound. The primary outcome is total pathological complete response rate. Secondary outcomes include breast pathological complete response rate, lymph node pathological complete response rate, objective response rate, event-free survival, distant disease-free survival, overall survival, and safety.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib Maleate; Drug: Trastuzumab (H, 8mg/kg; Drug: pegylated liposomal doxorubicin hydrochloride; Drug: Cyclophosphamide; Drug: Paclitaxel for Injection Albumin Bound

• Study Type: Interventional
• Enrollment (Estimated): 182
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhenchuan Song, MD; Phone Number: 18531117857; Email: songzhch@hotmail.com
• Study Contact Backup: Name: Lina Zhang, MD; Phone Number: +86 185 3111 7825

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Zhenchuan Song, MD; Phone Number: 185 31117857; Email: songzhch@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female patients aged 18 to 65 years.
• Patients with previously untreated invasive breast cancer confirmed by pathological examination.
• HER2-positive breast cancer, defined as immunohistochemistry (IHC) 3+ or IHC 2+ with HER2 gene amplification confirmed by in situ hybridization (ISH), regardless of hormone receptor status.
• Clinical stage T2N0-3M0 or any T/N1-N3M0 according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system.
• At least one measurable lesion according to RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function, meeting all of the following criteria:
• Hemoglobin ≥100 g/L.
• Absolute neutrophil count ≥1.5 × 10^9/L.
• Platelet count ≥100 × 10^9/L.
• Total bilirubin ≤1 × upper limit of normal (ULN).
• Alanine aminotransferase and aspartate aminotransferase ≤1.5 × ULN.
• Alkaline phosphatase ≤2.5 × ULN.
• Blood urea nitrogen and serum creatinine ≤1.5 × ULN.
• Left ventricular ejection fraction ≥55% by echocardiography.
• Women of childbearing potential must have a negative serum pregnancy test within 7 days before enrollment and agree to use appropriate contraception during the study and for 8 weeks after the last dose of study treatment.
• Patients must voluntarily participate in the study, sign the informed consent form, have good compliance, and be willing to cooperate with follow-up.

Exclusion Criteria:

• Prior receipt of any anti-tumor therapy, including chemotherapy, radiotherapy, molecular targeted therapy, or endocrine therapy.
• Concurrent receipt of any other anti-tumor therapy.
• Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer.
• Stage IV breast cancer.
• Breast cancer not confirmed by pathological examination.
• History of other malignancies within 5 years, except cured carcinoma in situ of the cervix.
• Severe dysfunction of major organs, including the heart, liver, or kidney.
• Inability to swallow, chronic diarrhea, intestinal obstruction, or other factors that may affect drug administration or absorption.
• Participation in another drug clinical trial within 4 weeks before enrollment.
• Known history of allergy to any component of the study treatment.
• History of immunodeficiency, including positive HIV test, hepatitis C virus infection, active hepatitis B virus infection, other acquired or congenital immunodeficiency diseases, or history of organ transplantation.
• History of any cardiac disease, including clinically significant arrhythmia requiring medication, myocardial infarction, heart failure, or any other cardiac disease judged by the investigator to make the patient unsuitable for this study.
• Pregnant or breastfeeding women, women of childbearing potential with a positive baseline pregnancy test, or women of childbearing potential unwilling to use effective contraception throughout the study.
• Serious concomitant diseases that, in the investigator's judgment, may compromise patient safety or affect completion of the study, including but not limited to uncontrolled severe hypertension, severe diabetes mellitus, or active infection.
• Clear history of neurological or psychiatric disorders, including epilepsy or dementia.
• Any other condition that, in the investigator's opinion, makes the patient unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pyrotinib Plus Trastuzumab and Neoadjuvant Chemotherapy; Participants will receive 8 cycles of neoadjuvant treatment. Pyrotinib maleate will be administered orally at 400 mg once daily from Day 1 of Cycle 1. Trastuzumab will be administered intravenously at a loading dose of 8 mg/kg in Cycle 1, followed by 6 mg/kg on Day 1 of each 3-week cycle. During the first 4 cycles, participants will receive pegylated liposomal doxorubicin hydrochloride 35 mg/m² and cyclophosphamide 600 mg/m² intravenously on Day 1 of each 3-week cycle. During the subsequent 4 cycles, participants will receive paclitaxel for injection albumin bound 230-260 mg/m² intravenously on Day 1 of each 3-week cycle.

Drug: Pyrotinib Maleate; Pyrotinib maleate will be administered orally at 400 mg once daily from Day 1 of Cycle 1. It should be taken within 30 minutes after breakfast and continued throughout the neoadjuvant treatment period.; Drug: Trastuzumab (H, 8mg/kg; Trastuzumab will be administered intravenously at a loading dose of 8 mg/kg on Day 1 of Cycle 1, followed by 6 mg/kg on Day 1 of each subsequent 3-week cycle during neoadjuvant treatment.; Drug: pegylated liposomal doxorubicin hydrochloride; Pegylated liposomal doxorubicin hydrochloride will be administered intravenously at 35 mg/m² on Day 1 of each 3-week cycle for the first 4 cycles of neoadjuvant treatment.; Drug: Cyclophosphamide; Cyclophosphamide will be administered intravenously at 600 mg/m² on Day 1 of each 3-week cycle for the first 4 cycles of neoadjuvant treatment in combination with pegylated liposomal doxorubicin hydrochloride, pyrotinib, and trastuzumab.; Drug: Paclitaxel for Injection Albumin Bound; Paclitaxel for injection albumin bound will be administered intravenously at 230-260 mg/m² on Day 1 of each 3-week cycle for the subsequent 4 cycles of neoadjuvant treatment in combination with pyrotinib and trastuzumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Pathological Complete Response Rate	Total pathological complete response is defined as the absence of residual invasive cancer in both the breast and axillary lymph nodes after neoadjuvant therapy.	At the time of surgery after completion of neoadjuvant therapy, approximately 24 weeks after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome Measure	Breast pathological complete response is defined as the absence of residual invasive cancer in the breast after neoadjuvant therapy.	At the time of surgery after completion of neoadjuvant therapy, approximately 24 weeks after treatment initiation
Lymph Node Pathological Complete Response Rate	Lymph node pathological complete response is defined as the absence of residual invasive cancer in axillary lymph nodes after neoadjuvant therapy.	At the time of surgery after completion of neoadjuvant therapy, approximately 24 weeks after treatment initiation
Objective Response Rate	Objective response rate is defined as the proportion of participants who achieve complete response or partial response according to RECIST version 1.1 during neoadjuvant therapy.	From baseline to completion of neoadjuvant therapy, approximately 24 weeks
Event-Free Survival	Event-free survival is defined as the time from enrollment to disease progression, recurrence, distant metastasis, second primary malignancy, or death from any cause, whichever occurs first.	From enrollment to the first documented event or death, assessed up to 3 years
Distant Disease-Free Survival	Distant disease-free survival is defined as the time from enrollment to the first occurrence of distant metastasis or death from any cause, whichever occurs first.	From enrollment to distant metastasis or death, assessed up to 3 years
Overall Survival	Overall survival is defined as the time from enrollment to death from any cause. Participants who are alive will be censored at the date of last follow-up.	From enrollment to death from any cause, assessed up to 3 years
Number of Participants With Adverse Events	Safety will be assessed by the incidence and severity of adverse events, graded according to NCI CTCAE version 5.0.	From the first dose of study treatment to 30 days after the last dose of neoadjuvant treatment

Collaborators and Investigators

• Sponsor: Hebei Medical University Fourth Hospital
• Investigators: Principal Investigator: Zhenchuan Song, Hebei Medical University Fourth Hospital

Publications and helpful links

General Publications

• Xuhong J, Qi X, Tang P, Fan L, Chen L, Zhang F, Tan X, Yan W, Zhong L, He C, Liang Y, Ren L, Wang M, Zhang Y, Jiang J. Neoadjuvant Pyrotinib plus Trastuzumab and Chemotherapy for Stage I-III HER2-Positive Breast Cancer: A Phase II Clinical Trial. Oncologist. 2020 Dec;25(12):e1909-e1920. doi: 10.1002/onco.13546. Epub 2020 Oct 20.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Neoadjuvant Therapy; Trastuzumab; Pyrotinib; Pathological Complete Response
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Physical Phenomena; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Taxoids; Cyclodecanes; Diterpenes; Elements; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Ions; Electrolytes; Gases; Elementary Particles; Cations, Monovalent; Cations; Hydrogen; Nucleons; Trastuzumab; Cyclophosphamide; Paclitaxel; Protons
• Other Study ID Numbers: OBU-BC-II-167

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 participant privacy protection, ethical considerations, and the absence of a pre-specified individual participant data sharing plan in the current study protocol.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No