Pyrotinib Versus Pertuzumab in Combination With Neoadjuvant Trastuzumab and Nab-Paclitaxel in HER2+ Early or Locally Advanced Breast Cancer

NCT ID: NCT04900311

Last Updated: 2021-05-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 490 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-31
• Study Completion Date: 2025-12-31

Brief Summary

The study is being conducted to evaluate the efficacy, and safety of pyrotinib versus pertuzumab in combination with trastuzumab and nab-paclitaxel for neoadjuvant treatment in HER2+ early or locally advanced breast cancer patients. To explore whether pyrotinib regimen could provide better clinical results compared with pertuzumab in the study population.

Detailed Description

This study is a multi-center, randomized, open-label, controlled trial. Eligible patients will be randomized to neoadjuvant pyrotinib or pertuzumab containing regimen every 3 weeks for four cycles before surgery. Randomization was stratified by the following factors: hormone receptor status and primary tumor size. After completing four cycles of neoadjuvant treatment, all patients who are eligible for surgery will undergo surgery and have their pathologic response evaluated. Following surgery, patients will receive 90-100 mg/m2 epirubicin and 600 mg/m2 cyclophosphamide every 3 weeks for 4 cycles. Clinicians will select subsequent treatments for patients based on guidelines as well as clinical practice at each site.

Conditions

HER2+ Early or Locally Advanced Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

pyrotinib + trastuzumab + nab-paclitaxel

Group Type: EXPERIMENTAL

pyrotinib + trastuzumab + nab-paclitaxel

Intervention Type: DRUG

patients will be treated every 3 weeks for four cycles prior to surgery at following doses: pyrotinib: 400 mg/day, orally, qd trastuzumab: IV infusion on Day 1 every 3 weeks with loading dose of 8 mg/kg in Cycle 1, and 6 mg/kg in Cycles 2-4 nab-paclitaxel: 260 mg/m2 IV infusion on Day 1 every 3 weeks, or 125 mg/m2 IV infusion on Days 1, 8 and 15 every 3 weeks (the nab-paclitaxel administration cycle was determined by investigator at each site)

pertuzumab + trastuzumab + nab-paclitaxel

Group Type: ACTIVE_COMPARATOR

pertuzumab + trastuzumab + nab-paclitaxel

Intervention Type: DRUG

patients will be treated every 3 weeks for four cycles prior to surgery at following doses: pertuzumab: IV infusion on Day 1 every 3 weeks with loading dose of 840 mg for Cycle 1, followed by 420 mg for Cycles 2-4 trastuzumab: IV infusion on Day 1 every 3 weeks with loading dose of 8 mg/kg in Cycle 1, and 6 mg/kg in Cycles 2-4 nab-paclitaxel: 260 mg/m2 IV infusion on Day 1 every 3 weeks, or 125 mg/m2 IV infusion on Days 1, 8 and 15 every 3 weeks (the nab-paclitaxel administration cycle was determined by investigator at each site)

Interventions

pyrotinib + trastuzumab + nab-paclitaxel

patients will be treated every 3 weeks for four cycles prior to surgery at following doses: pyrotinib: 400 mg/day, orally, qd trastuzumab: IV infusion on Day 1 every 3 weeks with loading dose of 8 mg/kg in Cycle 1, and 6 mg/kg in Cycles 2-4 nab-paclitaxel: 260 mg/m2 IV infusion on Day 1 every 3 weeks, or 125 mg/m2 IV infusion on Days 1, 8 and 15 every 3 weeks (the nab-paclitaxel administration cycle was determined by investigator at each site)

Intervention Type: DRUG

pertuzumab + trastuzumab + nab-paclitaxel

patients will be treated every 3 weeks for four cycles prior to surgery at following doses: pertuzumab: IV infusion on Day 1 every 3 weeks with loading dose of 840 mg for Cycle 1, followed by 420 mg for Cycles 2-4 trastuzumab: IV infusion on Day 1 every 3 weeks with loading dose of 8 mg/kg in Cycle 1, and 6 mg/kg in Cycles 2-4 nab-paclitaxel: 260 mg/m2 IV infusion on Day 1 every 3 weeks, or 125 mg/m2 IV infusion on Days 1, 8 and 15 every 3 weeks (the nab-paclitaxel administration cycle was determined by investigator at each site)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• female patients, treatment-naïve, aged ≥ 18 years and ≤ 75 years;
• ECOG score 0-1 (ECOG, Eastern Cooperative Oncology Group);
• Histologically confirmed invasive breast cancer (early stage or locally advanced) :Primary tumor greater than 2 cm diameter and cT2-cT4/cN0-cN3/cM0 (clinical stage II and III);
• HER2 expression positive breast cancer confirmed by pathological examination,
• known hormone receptor status (ER and PR);
• the level of major organ function must meet the following requirements: blood routine test: neutrophil (ANC) ≥ 1.5 × 109/L; platelet count (PLT) ≥ 90 × 109/L; hemoglobin (Hb) ≥ 90g/L; blood biochemistry test: total bilirubin (TBIL) ≤ 2.5 × ULN (upper normal limit); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; echocardiography: LVEF ((Left Ventricular Ejection Fraction) ≥ 55%; 12 ECG: QT interval corrected by Fridericia method (QTcF) < 470 ms in women
• Female subjects who have not yet experienced menopausal or not surgically sterile agree to practice abstinence or use effective methods of contraception for at least 7 months during and after the last dose of study drug;
• Sign the informed consent form and are willing to cooperate in the follow-up.

Exclusion Criteria

• breast cancer of both sides, stage IV breast cancer or metastatic breast cancer;
• inflammatory breast cancer;
• History of other malignancy, or previous anti-cancer therapy or radiotherapy for any malignancy, excluding cured carcinoma in situ of the cervix or squamous or basal cell carcinoma.
• simultaneously participated in other clinical trials;
• Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the patient has not fully recovered
• blood transfusion, or received colony-stimulating factor treatments before randomization;
• known history of allergy to any of the study medications and any of the ingredients or excipients of these medications;
• history of immunodeficiency, including positive HIV test, or suffering from other acquired, congenital immunodeficiency diseases, or history of organ transplantation.
• had any heart disease, including: (1) angina pectoris; (2) arrhythmia that is clinically significant or required medication; (3) myocardial infarction; (4) heart failure; (5) any other heart disease judged by the investigator as not suitable for this trial.
• pregnant or lactating
• Other concurrent serious diseases that are serious hazards to the patient's safety or may interfere with planned treatment (including but not limited to hypertension, severe diabetes, active infection, thyroid disease, etc.) ;
• Inability to swallow, chronic diarrhea, bowel obstruction, and other factors affecting medication intake and absorption.
• Any other condition that, in the opinion of the investigator, makes the subject unsuitable for this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: collaborator

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Jin Zhang, MD, Professor

Role: CONTACT

zhangjin@tjmuch.com

0086-22-23340123 ext. 2121

Other Identifiers

MA-BC-II-020

Identifier Type: -

Identifier Source: org_study_id