A Study of Pyrotinib Plus Vinorelbine in Comparison With Treatment of Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer

A Randomized, Multicenter, Phase II Open-label Study of the Efficacy and Safety of Pyrotinib + Vinorelbine vs. Treatment of Physician's Choice in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy

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 compare the safety and efficacy of Pyrotinib + vinorelbine vs. Treatment of Physician's Choice 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: Unknown
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib; Drug: vinorelbine; Drug: Treatment of physician's choice

• Study Type: Interventional
• Enrollment (Anticipated): 256
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results
• Histologically or cytologically confirmed invasive breast cancer
• 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
• 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pyrotinib 320mg + vinorelbine; pyrotinib 320mg tablets administered daily by mouth, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles	Drug: Pyrotinib; Pyrotinib Maleate combine with vinorelbine as the second-line treatment to HER2-positive Metastatic Breast Cancer; Drug: vinorelbine; vinorelbine
Experimental: pyrotinib 400mg + vinorelbine; pyrotinib 400mg tablets administered daily by mouth, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles	Drug: Pyrotinib; Pyrotinib Maleate combine with vinorelbine as the second-line treatment to HER2-positive Metastatic Breast Cancer; Drug: vinorelbine; vinorelbine
Experimental: Pyrotinib + vinorelbine; pyrotinib administered daily by mouth（MTD）, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatments will lasts until disease progression (as assessed by the investigator) or unmanageable toxicity.	Drug: Pyrotinib; Pyrotinib Maleate combine with vinorelbine as the second-line treatment to HER2-positive Metastatic Breast Cancer; Drug: vinorelbine; vinorelbine
Active Comparator: Treatment of physician's choice; Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and single-agent HER2-directed therapy.	Drug: Treatment of physician's choice; The treatment of physician's choice (TPC) was a protocol-specified approved or standard of care therapy or combination of therapies, based on frequently used regimens for second-line HER2-positive metastatic breast cancer treatment after receipt of trastuzumab-containing regimens. The therapies included single-agent chemotherapy, single-agent (e.g., tamoxifen or aromatase inhibitor) or dual-agent (e.g., aromatase inhibitor with luteinizing hormone releasing hormone [LHRH] agonist) hormonal therapy for hormone receptor positive-disease, and single-agent HER2-directed therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum-tolerated dose (MTD)	The maximum-tolerated dose (MTD) will be defined as the maximum dose level at which no more than one subject out of three experiences has a dose-limiting toxicity (DLT) upon completing two treatment cycle.	42 days
PFS as Assessed by the Investigator	progression-free survival	From enrollment to progression or death (for any reason),assessed up to 100 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	CR+PR	from enrollment to progression or death (for any reason), assessed up to 100 months
OS	OS was defined as the time from the date of randomization to the date of death from any cause	from enrollment to death (for any reason).assessed up to 100 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 15, 2019
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: June 13, 2019
• First Submitted That Met QC Criteria: June 24, 2019
• First Posted (Actual): June 25, 2019

Study Record Updates

• Last Update Posted (Actual): June 25, 2019
• Last Update Submitted That Met QC Criteria: June 24, 2019
• Last Verified: June 1, 2019

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; Vinorelbine
• Other Study ID Numbers: HR-BLTN-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No