Pyrotinib Plus Neoadjuvant Chemotherapy in HR+/HER2-, HER4-High Breast Cancer

NCT04872985 | Active Not Recruiting Phase 2

• 1 other identifier: MA-BC-II-018
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II, single-center, double-blind, placebo-controlled, randomized study of Pyrotinib in combination with Doxorubicin/Epirubicin and Cyclophosphamide followed by Docetaxel/nab-Paclitaxel as neoadjuvant therapy for women with hormone receptor positive HER2-negative stage II to III breast cancer. Patients randomized to the study arm/control arm will receive standard neoadjuvant chemotherapy in combination with pyrotinib/placebo, respectively. The primary endpoint of the study is the residual cancer burden 0/I (RCB 0/I) and total pathological complete response (tpCR) rate. Secondary endpoints include the breast pCR (bpCR) rate, objective response rate(ORR), event-free survival (EFS), overall survival (OS), rate of change in the Ki-67 proliferation index, correlations between potential biomarkers and treatment efficacy, and toxicity.

Conditions

Breast Cancer; Hormone-receptor Positive Breast Cancer

Keywords

Pyrotinib; Pan-HER TKI; HER4

Outcome Measures

Primary Outcomes (2)

• RCB 0/I (Residual cancer burden 0/I) rate

  defined as the proportion of patients whose surgical specimens after neoadjuvant therapy were pathologically assessed as RCB 0 or RCB I.

  At the time of surgery

• tpCR (total pCR) rate

  ypT0/isN0, number of participants with by no histologic evidence of invasive tumor cells in the surgical breast and axillary specimen.

  At the time of surgery.

Secondary Outcomes (9)

• bpCR (breast pCR)

  At the time of surgery.

• ORR (objective response) rate

  At the time of surgery.

• EFS (event-free survival) at 3 and 5 years

  EFS will be determined at 3 and 5 years after randomization

• OS (overall survival) at 3 and 5 years

  OS will be determined at 3 and 5 years after randomization

• Rate of change in the Ki-67 proliferation index

  Baseline and at the time of surgery

Study Arms (2)

Arm 1: Pyrotinib+ AC/EC followed by T

EXPERIMENTAL

400 mg Pyrotinib orally once per day with four cycles of epirubicin (100 mg/m2) (or doxorubicin hydrochloride liposome injection 30mg/m2) and cyclophosphamide (600 mg/m2) intravenously, once every 3 weeks, followed by four cycles of docetaxel (100 mg/m2) intravenously, once every 3 weeks (or 260mg/m2 nab-paclitaxel once every 3 weeks for 4 cycles, or 12 cycles of weekly nab-paclitaxel 120mg/m2 intravenously). Pyrotinib starts with a dose of 240 mg once daily for one week, followed by 320 mg once daily for the next week, before transitioning to 400 mg once daily as maintenance therapy.

Drug: Pyrotinib; Drug: Epirubicin; Drug: Doxorubicin Hydrochloride Liposome Injection; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Nab paclitaxel

Arm 2: Placebo+ AC/EC followed by T

PLACEBO COMPARATOR

400 mg placebo orally once per day with four cycles of epirubicin (100 mg/m2) (or doxorubicin hydrochloride liposome injection 30mg/m2) and cyclophosphamide (600 mg/m2) intravenously, once every 3 weeks, followed by four cycles of docetaxel (100 mg/m2) intravenously, once every 3 weeks (or 260mg/m2 nab-paclitaxel once every 3 weeks for 4 cycles, or 12 cycles of weekly nab-paclitaxel 120mg/m2 intravenously) .

Drug: Epirubicin; Drug: Doxorubicin Hydrochloride Liposome Injection; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Nab paclitaxel; Drug: Placebo

Interventions

Pyrotinib DRUG

400 mg orally once per day. Pyrotinib starts with a dose of 240 mg once daily for one week, followed by 320 mg once daily for the next week, before transitioning to 400 mg once daily as maintenance therapy.

Arm 1: Pyrotinib+ AC/EC followed by T

Epirubicin DRUG

100 mg/m2,q3W\*4

Also known as: E

Arm 1: Pyrotinib+ AC/EC followed by T; Arm 2: Placebo+ AC/EC followed by T

Doxorubicin Hydrochloride Liposome Injection DRUG

30mg/m2, q3w\*4

Also known as: A

Arm 1: Pyrotinib+ AC/EC followed by T; Arm 2: Placebo+ AC/EC followed by T

Cyclophosphamide DRUG

600 mg/m2, q3w\*4

Also known as: C

Arm 1: Pyrotinib+ AC/EC followed by T; Arm 2: Placebo+ AC/EC followed by T

Docetaxel DRUG

100 mg/m2, q3w\*4

Also known as: T

Arm 1: Pyrotinib+ AC/EC followed by T; Arm 2: Placebo+ AC/EC followed by T

Nab paclitaxel DRUG

120mg/m2 qw\*12 or 260mg/m2 q3w\*4

Arm 1: Pyrotinib+ AC/EC followed by T; Arm 2: Placebo+ AC/EC followed by T

Placebo DRUG

400 mg orally once per day

Arm 2: Placebo+ AC/EC followed by T

Eligibility Criteria

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

You may qualify if:

• Presenting with histological(by core needle biopsy or by limited incisional biopsy) proven hormone receptor positive (ER≥10% and/or PR ≥1%), HER2 negative(IHC ≤2+ and/or FISH-) , stage II/ III breast cancer.
• Have clinical indication for neoadjuvant therapy.
• HER4 IHC score ≥ 4.
• Measurable disease (breast and/or lymph nodes).
• The Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1.
• Adequate bone marrow function (within 4 weeks prior to registration): WBC≥3.0x109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l.
• Adequate liver function (within 4 weeks prior to registration): bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL.
• Adequate renal function (within 4 weeks prior to registration): the calculated creatinine clearance should be ≥50 ml/min.
• Patients must have the ability to swallow oral medication.
• Without history of any kind of treatment to known malignancy (solid tumor or hematologic).
• Written informed consent.
• Accessible for treatment and follow-up.

You may not qualify if:

• Evidence of stage IV breast cancer.
• Contralateral invasive breast cancer or Inflammatory breast cancer.
• History of non-breast malignancies (except for in situ cervical cancers, basal cell carcinoma of the skin, squamous cell carcinomas of the skin or thyroid papillary carcinoma that had received curative treatment before enrollment) within 5 years prior to randomization.
• Known metastatic disease from any malignancy (solid tumor or hematologic).
• Serious other diseases as infections (hepatitis B, C and HIV), recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias or on screening, any of the following cardiac parameters: bradycardia (heart rate \<50 at rest) or QTcF ≥450 msec.
• Known hypersensitivity reaction to any of the components of the treatment.
• Pregnancy or lactation at the time of randomization.
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

Study Sites (1)

Sun-Yat-Sen Memorial Hospital of Sun-Yat-Sen University

Guangzhou, Guangdong, 510120, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pyrotinib; Epirubicin; Cyclophosphamide; Docetaxel; Taxes

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Erwei Song, MD.,Phd.

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD.Ph.D.

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 5, 2021
• Study Start: April 20, 2021
• Primary Completion: February 27, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 6, 2026

Record last verified: 2025-09

Locations

CN (1)