Phase II Neoadjuvant Pyrotinib Combined With Neoadjuvant Chemotherapy in HER2-low-expressing and HR Positive Early or Locally Advanced Breast Cancer: a Single-arm, Non-randomized, Single-center, Open Label Trial

This is a single-arm, prospective, non-randomized, single-center, open label clinical study for evaluating the efficacy and safety of neoadjuvant pyrotinib combined with epirubicin and cyclophosphamide followed by docetaxel in HR positive and HER2-low-expressing early or locally advanced breast cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Neoadjuvant Therapy; Hormone Receptor-positive Breast Cancer; HER2-low-expressing Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib + epirubicin and cyclophosphamide followed by docetaxel treatment

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures
2. Female patients, age ≥ 18 years
3. Histologically confirmed unilateral primary carcinoma of the breast, except for occult breast cancer, inflammatory breast cancer without assessable focus or eczema like breast cancer
4. HER2-low-positive (defined here as HER2 IHC 2+ and FISH-) and HR positive(defined here as ER and/or PR >1% stained cells)
5. Tumour greater than 2 cm diameter or histologically (core- or fine-needle biopsy) involved lymph nodes
6. According to RECIST version 1.1, there is at least one evaluable target lesion
7. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
8. Required laboratory values including following parameters: WBC count:≥3.0 x 10^9/L ; ANC: ≥ 1.5 x 10^9/L; Platelet count: ≥ 100 x 10^9/L; Hemoglobin: ≥ 9.0 g/dL; Total bilirubin: ≤ 1.5 x upper limit of normal (ULN); ALT and AST: ≤ 2.5 x ULN; alkaline phosphatase ≤ 2.5 × ULN; Serum creatinine: ≤ 1.5 × ULN; Left ventricular ejection fraction (LVEF) ≥ 55%
9. For female patients without menopause or surgical sterilization: consent to contraception both during the trial and within 6 months after the last administration of the test drug

Exclusion Criteria:

1. Metastatic disease (Stage IV) or bilateral breast cancer
2. Known history of hypersensitivity to pyrotinib or any of it components
3. According to the judgment of the researcher, other anti-tumor treatments (except for ovarian function inhibitors) are required during neoadjuvant therapy
4. Patients with severe heart disease or discomfort who are expected to be unable to tolerate chemotherapy, including but not limited to these: 1). Fatal arrhythmia or higher grade atrioventricular block (second degree type 2 atrioventricular block or third degree atrioventricular block) 2). Unstable angina pectoris 3). Heart valve disease with clinical significance 4). ECG showed transmural myocardial infarction pain 5). Poor control of hypertension
5. Patients underwent major breast cancer-free surgery within 4 weeks or have not fully recovered
6. Serious or uncontrolled infections that may affect study treatment or evaluation of study results, including but not limited to active hepatitis virus infection, human immunodeficiency virus (HIV) antibody positive, lung infection, etc
7. History of other malignant tumors in the past 5 years (excluding cured carcinoma in situ of cervix or skin basal cell carcinoma)
8. Those with basic gastrointestinal diseases (especially long-term history of diarrhea or/and constipation)；Inability to swallow、intestinal obstruction or other factors will affect drug administration and absorption
9. The investigator believes that the patient has any other conditions that are not suitable for participation in the 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; Experimental: Patients will receive Pyrotinib combined with Epirubicin and Cyclophosphamide followed by Docetaxel	Drug: Pyrotinib + epirubicin and cyclophosphamide followed by docetaxel treatment; Drug: Pyrotinib pyrotinib 320mg orally daily Drug: Epirubicin epirubicin 90mg/m^2 d1 iv Q3W for 4 cycles Drug: Cyclophosphamide cyclophosphamide 600mg/m^2 d1 iv Q3W for 4 cycles Drug: Docetaxel docetaxel 100mg/m^2 d1 iv Q3W for 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual cancer burden 0/1 (RCB-0/1) rate	The percentage of patients with RCB-0/1 after neoadjuvant therapy	within 6 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response (pCR) rate	The percentage of patients with pCR (ypT0/is, ypN0) after neoadjuvant therapy	within 6 weeks after surgery
Objective response rate (ORR)	The percentage of subjects with CR or PR as the best response during the period from the beginning of the treatment to the progression of the disease or the completion of preoperative neoadjuvant therapy 【(CR+PR)/Analysis of the total number of people】	within 6 weeks after surgery
Breast conservation rate.	The breast conservation rate after treatment.	within 6 weeks after surgery
Disease-free Survival (DFS)	The DFS is defined as the time from registration until any relapse, secondary malignancy, or death from any cause	5 years
Overall Survival (OS).	The OS is defined as the time from registration to death, irrespective of cause.	5 years
Biomarkers	Biomarkers: e.g. Tils	5 years
Incidence of grade 3-5 diarrhea.	Diarrhea were graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.	before surgery

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Gong Chang, doctor, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2021
• Primary Completion (Actual): September 30, 2023
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: December 20, 2021
• First Submitted That Met QC Criteria: December 20, 2021
• First Posted (Actual): December 21, 2021

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Epirubicin
• Other Study ID Numbers: PILHLE-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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