Neoadjuvant Pyrotinib in HR-positive and HER2-low High-risk Early Breast Cancer

NCT06144944 | Active Not Recruiting Phase 3

• 1 other identifier: PILHLE-002
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, open-lable, prospective, randomized phase III clinical trial to further validate the efficacy and safety of neoadjuvant pyrotinib combined with chemotherapy in HR-positive/HER2-low (IHC 2+/FISH-negative) high-risk early breast cancer

Conditions

Breast Cancer Invasive; Hormone-receptor-positive Breast Cancer; HER2 Low Breast Carcinoma; Early-stage Breast Cancer

Keywords

pyrotintb; HER2-low EBC; neoadjuvant; HR-positive

Outcome Measures

Primary Outcomes (1)

• Residual Cancer Burden 0/1 rate as assessed by independent central review

  The proportion of patients with RCB 0/I after neoadjuvant therapy according to the online Residual Cancer Burden Calculator provided by the MD Anderson Cancer Center as assessed by independent central review

  Within 4 weeks after surgery

Secondary Outcomes (10)

• Residual Cancer Burden 0/1 rate as assessed by local pathology review

  Within 4 weeks after surgery

• Pathological complete response rate

  Within 4 weeks after surgery

• Objective response rate

  Within 2 weeks of breast MR examination

• Breast conservation surgery rate

  Within 4 weeks after surgery

• Health-related Quality of Life 1

  Within 7 days before the first treatment and the end of each cycle (each cycle is 21 days)

Study Arms (2)

Neoadjuvant pyrotinib combined with chemotherapy

EXPERIMENTAL

Drug: Pyrotinib, epirubicin or doxorubicin, cyclophosphamide, paclitaxel

Neoadjuvant chemotherapy

PLACEBO COMPARATOR

Drug: Epirubicin or doxorubicin, cyclophosphamide, paclitaxel

Interventions

Pyrotinib, epirubicin or doxorubicin, cyclophosphamide, paclitaxel DRUG

Pyrotinib 320 mg orally once daily, and epirubicin 90 mg/m² or doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² intravenously on day 1 for four 3-week cycles followed by paclitaxel 175 mg/m² intravenously on day 1 or four 3-week cycles.

Neoadjuvant pyrotinib combined with chemotherapy

Epirubicin or doxorubicin, cyclophosphamide, paclitaxel DRUG

Epirubicin 90 mg/m² or doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² intravenously on day 1 for four 3-week cycles followed by paclitaxel 175 mg/m² intravenously on day 1 or four 3-week cycles.

Neoadjuvant chemotherapy

Eligibility Criteria

• Age: 17 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Must participate voluntarily, sign the informed consent form, and have good compliance
• Aged ≥ 18 and ≤ 70 years old with ECOG PS score of 0-1
• Histopathological newly diagnosed, unilateral, primary invasive breast cancer
• Histopathological hormone receptor-positve ( estrogen receptor and/or progesterone receptor ≥ 10% stained cells) and HER2-low (immunochemistry 2+ with fluorescent in situ hybridization negative)
• TNM stage-IIb/III, or TNM stage-IIa with high risk (N+, G3, or MammaPrint High-risk)
• At least one evaluable target breast lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Left ventricular ejection fraction ≥ 55%, Fridericia-corrected QT interval \< 450 ms in males and \< 470 ms in females
• White blood cell count: ≥ 3.0 × 10\^9/L, absolute neutrophil count: ≥ 1.5 × 10\^9/L, platelet count: ≥ 100 × 10\^9/L, hemoglobin: ≥ 90 g/L
• Aspartate aminotransferase and alanine aminotransferase: ≤ 2.5 × ULN, alkaline phosphatase: ≤ 2.5 × ULN, blood total bilirubin: ≤ 1.5 × ULN, serum creatinine: ≤ 1.5 × ULN
• Non-menopausal or non-surgically sterilized female patients identified as non-pregnant and non-lactating and consented to contraception both during the trial and within 6 months after the last administration of the test drug

You may not qualify if:

• Metastatic BC, bilateral BC, occult BC, inflammatory BC, or with other malignant tumors
• Known history of hypersensitivity to the study drugs
• Patients who need receive other anti-tumor treatments (except for OFS) during neoadjuvant therapy as judged by the investigators
• With severe cardiac disease or discomfort that is not expected to tolerate treatment, including but not limited to: a) arrhythmia that requires medication or is clinically significant, or high-grade atrioventricular block, b) unstable angina, myocardial infarction, heart failure or clinically significant heart valve disease, c) poorly controlled hypertension or any heart disease unsuitable for participation in this trial as determined by the investigators
• Patients who participated in a clinical trial of another drug within 4 weeks prior to randomization or underwent BC-free surgery within 4 weeks or had not fully recovered after BC-free surgery
• Other malignancy in the past 5 years, other than cured cervical carcinoma in situ, basal or squamous cell carcinoma of skin
• Patients who had basic gastrointestinal diseases (especially long-term history of diarrhea or/and constipation), inability to swallow, intestinal obstruction or other factors will affect drugs administration and absorption
• Presence of accompanying diseases that may pose serious risks to the safety of the patient or may affect the patient's ability to complete the study (including but not limited to severe diabetes mellitus, active infection, thyroid disorders, etc.) as judged by the investigator
• With a history of immunodeficiency, including acquired or congenital immunodeficiencies, or a history of organ transplantation
• Past history of confirmed neurological or mental disorders, including epilepsy or dementia
• Other conditions of the subject determined by the investigator to be unsuitable for the study

Sponsors & Collaborators

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

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; Doxorubicin; Cyclophosphamide; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Chang Gong, Prof

  Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: November 22, 2023
• Study Start: January 17, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2031
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: beginning 3 months and ending 5 years following publication of future research article
• Access Criteria: Researchers who provide a methodologically sound proposal, that need to be approved by an approved accredited ethics committee

Locations

CN (1)