Neoadjuvant Chemotherapy With Pyrotinib, Epirubicin and Cyclophosphamide Followed by Taxanes and Trastuzumab for HER-2+ Breast Cancer

Neoadjuvant Chemotherapy With Pyrotinib, Epirubicin and Cyclophosphamide Followed by Taxanes and Trastuzumab for HER2+Breast Cancer: a Multicenter, Randomized, Open-label, Parallel-Group Controlled Trial

This is a prospective, open label, parallel controlled study to evaluate the efficacy and safety of neoadjuvant pyrotinib in HER2+ breast cancer patients

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Taxanes; Biological: Trastuzumab

• Study Type: Interventional
• Enrollment (Anticipated): 280
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: YUNJIANG LIU, PHD.; Phone Number: 86095588; Email: lyj818326@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female breast cancer patients at the age of >= 18 years and <= 65 years who received first treatment；
2. Pathologically confirmed HER2-positive invasive breast cancer（which is defined as the immunohistochemistry score of > 10% immunoreactive cells being 3+ or in situ hybridization results showing HER2 gene amplification），regardless of hormone receptor status (ER and PR)；
3. According to the 2019 CSCO BC guidelines: When HER-2 positive is used as the standard for preoperative neoadjuvant therapy for breast cancer, the tumor is larger than 2 cm；
4. The Eastern Tumor Collaborative Group (ECOG) has a physical status score of ≤1；
5. The functional level of the main organs must meet the following requirements ： 1) blood routine test: hemoglobin (Hb) ≥ 90g/L;Neutrophils (ANC) ≥ 1.5 × 10^9/L; platelet count (PLT) ≥ 90 × 10^9/L; 2) Blood biochemistry: Total bilirubin (TBIL) ≤ 1.5 upper limit of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; Urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; 3) Heart color ultrasound: Left ventricular ejection fraction (LVEF) ≥ 55%;
6. Women of childbearing age, tested negative for serum pregnancy test 7 days before randomization，and willing to use appropriate methods during the trial and within 8 weeks after the last administration of the test drug;
7. A volunteer to participate in the study; provision of written informed consent; good compliance and willing to cooperate during the follow-up.

Exclusion Criteria:

1. Known history of hypersensitivity to pyrotinib or any of it components;
2. Patients have previously received antitumor treatment or radiation therapy for any malignant tumor (except for cervical carcinoma in situ and basal cell carcinoma that have been cured);
3. Patients underwent major breast cancer-free surgery within 4 weeks and have not fully recovered;
4. Subjects that are unable to swallow tablets,intestinal obstruction or dysfunction of gastrointestinal absorption;
5. Patients with severe heart disease or discomfort who cannot be treated;
6. The patient suffers from mental illness or psychotropic substance abuse and cannot cooperate;
7. Pregnant or lactating women;
8. Less than 4 weeks from the last clinical trial;
9. Patients participating in other clinical trials at the same time
10. The researchers think inappropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Patients will receive the test drug (Pyrotinib) combined with Epirubicin and Cyclophosphamide followed by Taxanes and Trastuzumab	Drug: Pyrotinib; 400mg administered as continuous oral once daily from the first day of the study; Drug: Epirubicin; 90mg/m^2 d1 iv Q2W for 4 cycles; Drug: Cyclophosphamide; 600 mg/m^2 d1 iv Q2W for 4 cycles; Drug: Taxanes; Albumin paclitaxel（125mg/m2 d1、8 iv Q3W for 4 Cycles）/Docetaxel(100mg/m2 d1 iv Q3W for 4 Cycles ); Biological: Trastuzumab; the first cycle is a loading dose of 8 mg / kg, followed by 6 mg / kg. Iv Q3W for 1 year
Active Comparator: Control group; Patients will only receive Epirubicin and Cyclophosphamide followed by Taxanes and Trastuzumab	Drug: Epirubicin; 90mg/m^2 d1 iv Q2W for 4 cycles; Drug: Cyclophosphamide; 600 mg/m^2 d1 iv Q2W for 4 cycles; Drug: Taxanes; Albumin paclitaxel（125mg/m2 d1、8 iv Q3W for 4 Cycles）/Docetaxel(100mg/m2 d1 iv Q3W for 4 Cycles ); Biological: Trastuzumab; the first cycle is a loading dose of 8 mg / kg, followed by 6 mg / kg. Iv Q3W for 1 year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response rate(pCR)	pathological complete response	within 3 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate(ORR)	Baseline to measured stable disease	2 years
Event Free Survival(EFS)	Baseline to the occurrence of any event	3 years
Disease-free survival(DFS) Baseline to measured date of recurrence or death from any cause	Baseline to measured date of recurrence or death from any cause	3 years
Overall survival (OS)	Baseline to measured date of death from any cause	5 years

Collaborators and Investigators

• Sponsor: Hebei Medical University Fourth Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2020
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: February 27, 2020
• First Submitted That Met QC Criteria: February 27, 2020
• First Posted (Actual): March 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 2, 2020
• Last Update Submitted That Met QC Criteria: February 27, 2020
• Last Verified: February 1, 2020

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; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Trastuzumab; Epirubicin; Taxane
• Other Study ID Numbers: HRHB-CB001

Drug and device information, study documents

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