Back to resultsA Study of Pyrotinib Plus Vinorelbine in Comparison With Treatment of Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer
Primary Purpose
Metastatic Breast Cancer
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Pyrotinib
Treatment of physician's choice
vinorelbine
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
pyrotinib 320mg + vinorelbine
pyrotinib 400mg + vinorelbine
Pyrotinib + vinorelbine
Treatment of physician's choice
Arm Description
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
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
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.
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.
Outcomes
Primary Outcome Measures
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.
PFS as Assessed by the Investigator
progression-free survival
Secondary Outcome Measures
Objective Response Rate
CR+PR
OS
OS was defined as the time from the date of randomization to the date of death from any cause
Full Information
NCT ID
NCT03997539
First Posted
June 13, 2019
Last Updated
June 24, 2019
Sponsor
Sun Yat-sen University
Collaborators
Jiangsu HengRui Medicine Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03997539
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Unknown status
Study Start Date
August 15, 2019 (Anticipated)
Primary Completion Date
June 30, 2021 (Anticipated)
Study Completion Date
December 30, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
Collaborators
Jiangsu HengRui Medicine Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
256 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
pyrotinib 320mg + vinorelbine
Arm Type
Experimental
Arm Description
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
Arm Title
pyrotinib 400mg + vinorelbine
Arm Type
Experimental
Arm Description
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
Arm Title
Pyrotinib + vinorelbine
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment of physician's choice
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pyrotinib
Intervention Description
Pyrotinib Maleate combine with vinorelbine as the second-line treatment to HER2-positive Metastatic Breast Cancer
Intervention Type
Drug
Intervention Name(s)
Treatment of physician's choice
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
vinorelbine
Intervention Description
vinorelbine
Primary Outcome Measure Information:
Title
maximum-tolerated dose (MTD)
Description
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.
Time Frame
42 days
Title
PFS as Assessed by the Investigator
Description
progression-free survival
Time Frame
From enrollment to progression or death (for any reason),assessed up to 100 months
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
CR+PR
Time Frame
from enrollment to progression or death (for any reason), assessed up to 100 months
Title
OS
Description
OS was defined as the time from the date of randomization to the date of death from any cause
Time Frame
from enrollment to death (for any reason).assessed up to 100 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
12. IPD Sharing Statement
Learn more about this trial
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
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