Nab-paclitaxel in Combination With Pyrotinib in Postoperative Adjuvant Therapy for HER2-positive Breast Cancer

A Multicenter, Open-label, Single-arm, Phase II Clinical Trial of Nab-paclitaxel in Combination With Pyrotinib in Adjuvant Therapy for Lymph Node-negative and Small Tumor HER2-positive Breast Cancer

This is a multicenter, open-label, single-arm, prospective, phase II study. conducted to evaluate the efficacy, safety and tolerability of nab-paclitaxel plus pyrotinib in patients with lymph node-negative and tumor size ≤3 cm, HER2 positive breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Early Breast Cancer
• Intervention / Treatment: Drug: Nab-paclitaxel in combination with pyrotinib

• Study Type: Interventional
• Enrollment (Anticipated): 261
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qiang Sun, MD; Phone Number: +861069152700; Email: sunqiangpumc@sina.com
• Study Contact Backup: Name: Changjun Wang, MD; Phone Number: +861069158721; Email: wangchangjun@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Enrollment subjects must have a pathological diagnosis of HER2-positive primary invasive breast cancer with an immunohistochemistry (IHC) score of 3 +, or 2 + and HER2 gene amplification by in situ hybridization (ISH) (ratio of HER2/CEP17 ≥ 2.0).
• The invasive tumor had to measure no more than 3cm and with histologically confirmed lymph node-negative or one lymph node micrometastasis (T ≤ 3 cm, N0/N1mi, M0).
• Tumor should has known ER/PR hormone receptor status.
• All patients must be women above18 years old with Eastern Cooperative Oncology Group score 0 to 1.
• Adequate hematopoietic function and organ function as defined as follows: neutrophil count ≥ 1.5 x 109/L; Platelet count ≥ 90 × 109/L; Hemoglobin ≥ 90 g/L; total bilirubin ≤ 1.5 × ULN; alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3 × ULN; serum creatinine Cr ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula).
• left ventricular ejection fraction (LVEF) ≥ 50% and Electrocardiogram Fridericia-corrected QT interval (QTcF) ≤ 480 ms.
• Provide written informed consent.

Exclusion Criteria:

• Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease prior to or at the time of study entry.
• Previous treatment with chemotherapeutic drugs, or tyrosine kinase inhibitors targeting HER2 (lapatinib, neratinib or pyrotinib, etc.).
• Other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma.
• Inability to swallow, chronic diarrhea, or intestinal obstruction.
• Known to be allergic to the drug components.
• Have a history of immunodeficiency, including HIV positive, HCV positive, active viral hepatitis B or other immunodeficiency diseases.
• Have a history of organ transplantation.
• Pregnant, lactating female patients, or female patients who are unwilling to take effective contraceptive.
• Any heart disease, including: (1) arrhythmia; (2) myocardial infarction; (3) heart failure.
• Any other concomitant diseases assessed by investigator as unsuitable for study.
• Previous history of definite neurological or psychiatric disorders.
• Concomitant use of CYP3A4 inhibitors or inducers or drugs that prolong the QT interval.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Nab-paclitaxel in combination with pyrotinib treatment group; Nab-paclitaxel 260mg/m2 every 3 weeks for 12 weeks plus pyrotinib 240mg daily for one year	Drug: Nab-paclitaxel in combination with pyrotinib; Nab-paclitaxel I.V. 260mg/m2 every 3 weeks for 12 weeks plus pyrotinib oral 240mg daily for one year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year-DFS	3-years-disease free survival rate	From the start of treatment to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs+SAEs	Adverse Events and Serious Adverse Events are described in terms of CTC AE 5.0	from the first drug administration to within 28 days for the last pyrotinib dose

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• Wang C, Zhou Y, Lin Y, Mao F, Guan J, Zhang X, Shen S, Wang X, Zhang Y, Pan B, Zhong Y, Peng L, Cao X, Yao R, Zhou X, Xu C, Xu Y, Sun Q. Rationale and design of a phase II trial of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for N0/N1mi, HER2 + early breast cancer (PHAEDRA). BMC Cancer. 2022 Mar 14;22(1):269. doi: 10.1186/s12885-022-09346-1.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2021
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2025

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (ACTUAL): December 9, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 9, 2020
• Last Update Submitted That Met QC Criteria: December 2, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: MA-BC-II-007

Drug and device information, study documents

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