Pyrotinib Plus Vinorelbine in Participants With HER2-positive Previously Treated Locally Advanced or Metastatic Breast Cancer

A Single-arm, Multi-center Phase II Clinical Study of Pyrotinib Combined With Vinorelbine in the Treatment of HER2-positive and Treated Metastatic Breast Cancer

The purpose of this study is to identify the highest tolerable dose of pyrotinib in combination with vinorelbine and to assess the safety and efficacy of the combination in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer.

The study will be conducted in two parts. In the first part, testing will be done on up to 12 subjects to determine the highest tolerable dose of pyrotinib and vinorelbine in patients with advanced solid tumors. In the second part of the study, we will explore the safety and efficacy of Pyrotinib + vinorelbine in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy. Participants will be treated until disease progression (PD), unmanageable toxicity, or study termination.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Breast Diseases; HER2-positive Breast Cancer; Vinorelbine; Pyrotinib
• Intervention / Treatment: Drug: Pyrotinib 320mg + Vinorelbine; Drug: Pyrotinib 400mg + Vinorelbine; Drug: Pyrotinib plus Vinorelbine

• Study Type: Interventional
• Enrollment (Anticipated): 208
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: wang shusen; Phone Number: +86-13926168469; Email: wangshs@sysucc.org.cn
• Study Contact Backup: Name: zhang jingmin; Phone Number: +8618826246924; Email: zhangjm1@sysucc.org.cn

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • Zhang Jingmin
    • Contact: zhang jingmin; Phone Number: +8618826246924; Email: zhangjm1@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed invasive breast cancer
• HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results
• Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or metastatic setting must include both a taxane, alone or in combination with another agent, and trastuzumab, alone or in combination with another agent. Patients who have previously used pertuzumab will be allowed.
• Documented progression (which occur during or after most recent treatment or within 6 months after completing of adjuvant therapy) of incurable, unresectable, locally advanced or metastatic breast cancer, defined by the investigator
• Measurable and/or nonmeasurable disease; participants with central nervous system-only disease are excluded
• Cardiac ejection fraction greater than or equal to (>/=) 50 percent (%) by either echocardiogram or multi-gated acquisition scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• History of treatment with pyrotinib
• Prior treatment with lapatinib or neratinib
• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma
• History of receiving any anti-cancer drug/biologic or investigational treatment within 28 days prior to randomization except hormone therapy
• Recovery of treatment-related toxicity consistent with other eligibility criteria
• History of radiation therapy within 28 days of randomization
• Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months (60 days) of randomization
• History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction or unstable angina
• Current severe, uncontrolled systemic disease (for example, clinically significant cardiovascular, pulmonary, or metabolic disease)
• Pregnancy or lactation
• Current known active infection with human immunodeficiency virus (HIV) or hepatitis C virus
• Presence of conditions that could affect gastrointestinal absorption: Malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis

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: Pyrotinib plus vinorelbine

Drug: Pyrotinib 320mg + Vinorelbine; pyrotinib 320mg tablets administered daily by mouth, vinorelbine(po) 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles; Drug: Pyrotinib 400mg + Vinorelbine; pyrotinib 400mg tablets administered daily by mouth, vinorelbine(po) 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles; Drug: Pyrotinib plus Vinorelbine; pyrotinib administered daily by mouth（MTD）, vinorelbine(po) 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered on day 1 and day 8 of 21 day cycle, or vinorelbine(iv) 25 mg/m2 on day 1 and day 8 of 21 day cycle. Treatments will lasts until disease progression (as assessed by the investigator) or unmanageable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS as Assessed by the Investigator	Progression-Free Survival	from enrollment to progression or death (for any reason), assessed up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	from enrollment to progression or death (for any reason), assessed up to 3 years	Ratio of CR and PR in all subjects
OS	OS was defined as the time from the date of randomization to the date of death from any cause.	from enrollment to progression or death (for any reason), assessed up to 3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Publications and helpful links

General Publications

• Ma F, Ouyang Q, Li W, Jiang Z, Tong Z, Liu Y, Li H, Yu S, Feng J, Wang S, Hu X, Zou J, Zhu X, Xu B. Pyrotinib or Lapatinib Combined With Capecitabine in HER2-Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab: A Randomized, Phase II Study. J Clin Oncol. 2019 Oct 10;37(29):2610-2619. doi: 10.1200/JCO.19.00108. Epub 2019 Aug 20.
• Li X, Yang C, Wan H, Zhang G, Feng J, Zhang L, Chen X, Zhong D, Lou L, Tao W, Zhang L. Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur J Pharm Sci. 2017 Dec 15;110:51-61. doi: 10.1016/j.ejps.2017.01.021. Epub 2017 Jan 21.
• Ma F, Li Q, Chen S, Zhu W, Fan Y, Wang J, Luo Y, Xing P, Lan B, Li M, Yi Z, Cai R, Yuan P, Zhang P, Li Q, Xu B. Phase I Study and Biomarker Analysis of Pyrotinib, a Novel Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. J Clin Oncol. 2017 Sep 20;35(27):3105-3112. doi: 10.1200/JCO.2016.69.6179. Epub 2017 May 12.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 22, 2020
• Primary Completion (ANTICIPATED): August 1, 2023
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: October 22, 2020
• First Posted (ACTUAL): October 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 24, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Neoplasms; Breast Diseases; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Vinorelbine
• Other Study ID Numbers: MA-BC-II-002

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