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

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03997539
• Other study ID #: HR-BLTN-002
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 15, 2019
• Est. completion date: December 30, 2021

Study information

• Verified date: June 2019
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 256
• Est. completion date: December 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Pyrotinib
Pyrotinib Maleate combine with vinorelbine as the second-line treatment to HER2-positive Metastatic Breast Cancer
• 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.
• vinorelbine
vinorelbine

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	Jiangsu HengRui Medicine Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	PFS as Assessed by the Investigator	progression-free survival	From enrollment to progression or death (for any reason),assessed up to 100 months
Secondary	Objective Response Rate	CR+PR	from enrollment to progression or death (for any reason), assessed up to 100 months
Secondary	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