Back to resultsPyrotinib Combined With Trastuzumab and AI in the First-line Treatment of HER2 Positive/ HR Positive MBC (Pyrotinib)
Primary Purpose
Breast Cancer Female, HER2-positive Breast Cancer, Hormone Receptor Positive Malignant Neoplasm of Breast
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Pyrotinib
Trastuzumab
Aromatase inhibitor
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer Female focused on measuring MBC, Pyrotinib, Trastuzumab, First line, HER2
Eligibility Criteria
Inclusion Criteria:
- Age≥18 years, female;
- Postmenopausal or pre-menopausal with ovarian function suppression;
- At least one measurable lesion evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1;
- Metastatic or inoperable local advanced breast cancer;
- HER2-positive breast cancer;
- HR-positive breast cancer;
- LVEF ≥50%;
Exclusion Criteria:
- Previous systemic non-hormonal anticancer therapy in the metastatic or advanced breast cancer setting;
- Received endocrine therapy within 7 days before randomization;
- Uncontrolled central nervous system metastases;
- Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months.
- Other malignancies within the last 3 years, except for carcinoma in situ of the cervix or basal cell carcinoma.
- Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
- Severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease, which leading to a clinical indication for chemotherapy.
- History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia);
- History of myocardial infarction within 6 months of randomization
- History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
- Pregnant or lactating women;
- QT interval>470 ms；
- Serious concomitant diseases (including severe hypertension, severe diabetes, active infection, thyroid disease, etc.) that are harmful to the patient's safety or affect the patient's completion of the study;
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Pyrotinib and trastuzumab plus aromatase inhibitor
Trastuzumab plus aromatase inhibitor
Arm Description
Participants will receive pyrotinib in combination with trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Participants will receive trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS)
PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or death from any cause, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
The PFS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median PFS, hazard ratio with appropriate confidence intervals will be reported.
Secondary Outcome Measures
Overall Survival (OS)
Overall Survival (OS), defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication and participants with no post-baseline information were censored at the date of randomization.
The OS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median OS, hazard ratio with appropriate confidence intervals will be reported.
Objective Overall Response Rate (ORR)
ORR was defined as percentage of participants with best (confirmed) overall response (BOR) of either CR or PR. ORR was assessed by the investigator according to RECIST version 1.1 and is based on BOR, which is defined as best response recorded from start of study treatment until disease progression/recurrence or death. Participants needed to have two consecutive assessments of PR or CR to be a responder. Only participants with measurable disease at baseline were included in the analysis of BOR and who did not have any evaluable post-baseline assessments were classified as not evaluable.
The ORR will be reported by percentage with each arms and appropriate confidence intervals.
Duration of Response (DoR)
DoR is defined as date of initial confirmed PR/CR until date of progressive disease or death from any cause. PR or CR or SD is according to RECIST version 1.1.
The DoR will be estimated using Kaplan-Meier method. Kaplan-Meier curves, median DoR, hazard ratio with appropriate confidence intervals will be reported.
Time to Response (TTR)
Time to Response (TTR), defined as the time from the date of randomization to the date of first CR or PR. CR or PR is according to RECIST version 1.1.
The TTR will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median TTR, hazard ratio with appropriate confidence intervals will be reported.
Clinical Benefit Response (CBR)
CBR is percentage of participants with best (confirmed) PR or CR or SD for at least 6 months. PR or CR or SD is according to RECIST version 1.1.
The CBR will be reported by percentage with each arms and appropriate confidence intervals.
Adverse events (AEs)
AEs were graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.3.
In general, AEs are graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE.
The type, grade and frequency of AEs will be reported.
Quality of Life (QoL) by FACT-B
QoL was assessed using Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B). FACT-B is a 37-item questionnaire with 5 subscales assessing physical, social, emotional, and functional well-being, as well as a breast cancer specific subscale.
FACT-B questionnaires were completed by patients on screening phase (baseline) and each 6 weeks after randomization. Mean change from baseline of FACT-B scores by each visit for each arms will be reported.
Quality of Life (QoL) by EQ-5D
QoL was assessed using EuroQoL 5-Dimensions (EQ-5D). EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments.
EQ-5D questionnaires were completed by patients on screening phase (baseline) and each 6 weeks after randomization. Mean change from baseline of EQ-5D scores by each visit for each arms will be reported.
Full Information
NCT ID
NCT03910712
First Posted
April 3, 2019
Last Updated
April 9, 2019
Sponsor
Peking Union Medical College Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03910712
Brief Title
Pyrotinib Combined With Trastuzumab and AI in the First-line Treatment of HER2 Positive/ HR Positive MBC
Acronym
Pyrotinib
Official Title
A Randomized, Open-label Study of First Line Pyrotinib, Trastuzumab With an Aromatase Inhibitors, in the Treatment of HER2 Positive and HR Positive Metastatic or Inoperable Locally Advanced Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 1, 2019 (Anticipated)
Primary Completion Date
June 1, 2022 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking Union Medical College Hospital
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a randomized, open-label, phase II study, comparing the efficacy and safety of trastuzumab plus aromatase inhibitors, with or without pyrotinib, in the treatment of HR (hormone receptor)+/HER2 (human epidermal growth factor receptor 2) + MBC and inoperable LABC patients.
Detailed Description
This is a randomized, two-arm, open-label, multicenter phase II trial. Our primary purpose is to compare that PFS of patients with trastuzumab, AI plus pyrotinib and trastuzumab plus an AI for HER2-positive and hormone receptor-positive MBC or locally advanced breast cancer (LABC).
Eligible patients will randomized to a ratio of 1:1 to pyrotinib+ trastuzumab + aromatase inhibitor (experimental group) or trastuzumab+aromatase inhibitor (control group). Stratification factors were 1)time since adjuvant hormone therapy (<=12 months/>12 months/no prior hormone therapy); 2) lesion (visceral; non-visceral).
In treatment period, patients will be administrated trastuzumab plus aromatase inhibitors, with or without pyrotinib, every 21 days for 1 cycle, until disease progression, toxicity intolerance, withdrawal of informed consent, patients judged must be terminated study termination.
The imaging evaluation was performed according to the RECIST 1.1 criteria every 6 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer Female, HER2-positive Breast Cancer, Hormone Receptor Positive Malignant Neoplasm of Breast, Metastatic Breast Cancer, Breast Diseases, Hormone Receptor Positive Tumor
Keywords
MBC, Pyrotinib, Trastuzumab, First line, HER2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
250 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pyrotinib and trastuzumab plus aromatase inhibitor
Arm Type
Experimental
Arm Description
Participants will receive pyrotinib in combination with trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Arm Title
Trastuzumab plus aromatase inhibitor
Arm Type
Active Comparator
Arm Description
Participants will receive trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Intervention Type
Drug
Intervention Name(s)
Pyrotinib
Other Intervention Name(s)
Study drug
Intervention Description
Pyrotinib were administered 400 mg orally daily. Oral administration within 30 minutes after breakfast, and continuous administration for 21 days for 1 cycle.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin®
Intervention Description
Trastuzumab were administered every 3 weeks intravenously (8 mg/kg loading doses followed by 6 mg/kg maintenance doses).
Intervention Type
Drug
Intervention Name(s)
Aromatase inhibitor
Other Intervention Name(s)
anastrozole, letrozole or exemestane
Intervention Description
The investigator chose an aromatase inhibitor (either anastrozole, letrozole or exemestane 1 mg/2.5 mg/25 mg), once daily, oral.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or death from any cause, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
The PFS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median PFS, hazard ratio with appropriate confidence intervals will be reported.
Time Frame
From randomization to 36 month
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall Survival (OS), defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication and participants with no post-baseline information were censored at the date of randomization.
The OS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median OS, hazard ratio with appropriate confidence intervals will be reported.
Time Frame
From randomization to 36 month
Title
Objective Overall Response Rate (ORR)
Description
ORR was defined as percentage of participants with best (confirmed) overall response (BOR) of either CR or PR. ORR was assessed by the investigator according to RECIST version 1.1 and is based on BOR, which is defined as best response recorded from start of study treatment until disease progression/recurrence or death. Participants needed to have two consecutive assessments of PR or CR to be a responder. Only participants with measurable disease at baseline were included in the analysis of BOR and who did not have any evaluable post-baseline assessments were classified as not evaluable.
The ORR will be reported by percentage with each arms and appropriate confidence intervals.
Time Frame
From randomization to 36 month
Title
Duration of Response (DoR)
Description
DoR is defined as date of initial confirmed PR/CR until date of progressive disease or death from any cause. PR or CR or SD is according to RECIST version 1.1.
The DoR will be estimated using Kaplan-Meier method. Kaplan-Meier curves, median DoR, hazard ratio with appropriate confidence intervals will be reported.
Time Frame
From randomization to 36 month
Title
Time to Response (TTR)
Description
Time to Response (TTR), defined as the time from the date of randomization to the date of first CR or PR. CR or PR is according to RECIST version 1.1.
The TTR will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median TTR, hazard ratio with appropriate confidence intervals will be reported.
Time Frame
From randomization to 36 month
Title
Clinical Benefit Response (CBR)
Description
CBR is percentage of participants with best (confirmed) PR or CR or SD for at least 6 months. PR or CR or SD is according to RECIST version 1.1.
The CBR will be reported by percentage with each arms and appropriate confidence intervals.
Time Frame
From randomization to 36 month
Title
Adverse events (AEs)
Description
AEs were graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.3.
In general, AEs are graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE.
The type, grade and frequency of AEs will be reported.
Time Frame
From screening phase until AEs returns to Grade 0-1 or baseline
Title
Quality of Life (QoL) by FACT-B
Description
QoL was assessed using Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B). FACT-B is a 37-item questionnaire with 5 subscales assessing physical, social, emotional, and functional well-being, as well as a breast cancer specific subscale.
FACT-B questionnaires were completed by patients on screening phase (baseline) and each 6 weeks after randomization. Mean change from baseline of FACT-B scores by each visit for each arms will be reported.
Time Frame
From randomization to 36 month
Title
Quality of Life (QoL) by EQ-5D
Description
QoL was assessed using EuroQoL 5-Dimensions (EQ-5D). EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments.
EQ-5D questionnaires were completed by patients on screening phase (baseline) and each 6 weeks after randomization. Mean change from baseline of EQ-5D scores by each visit for each arms will be reported.
Time Frame
From randomization to 36 month
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age≥18 years, female;
Postmenopausal or pre-menopausal with ovarian function suppression;
At least one measurable lesion evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1;
Metastatic or inoperable local advanced breast cancer;
HER2-positive breast cancer;
HR-positive breast cancer;
LVEF ≥50%;
Exclusion Criteria:
Previous systemic non-hormonal anticancer therapy in the metastatic or advanced breast cancer setting;
Received endocrine therapy within 7 days before randomization;
Uncontrolled central nervous system metastases;
Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months.
Other malignancies within the last 3 years, except for carcinoma in situ of the cervix or basal cell carcinoma.
Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
Severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease, which leading to a clinical indication for chemotherapy.
History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia);
History of myocardial infarction within 6 months of randomization
History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
Pregnant or lactating women;
QT interval>470 ms；
Serious concomitant diseases (including severe hypertension, severe diabetes, active infection, thyroid disease, etc.) that are harmful to the patient's safety or affect the patient's completion of the study;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qiang Sun, M.D.
Phone
86-10-69158721
Email
sunqiangpumch@sina.com
First Name & Middle Initial & Last Name or Official Title & Degree
Changjun Wang, M.D.
Phone
86-10-69158721
Email
wcj_sumy@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qiang Sun, M.D.
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32660609
Citation
Wang C, Lin Y, Zhou Y, Mao F, Zhu H, Guan J, Zhang X, Shen S, Huang X, Chen C, Yao R, Zhao J, Sun Q. Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial. BMC Cancer. 2020 Jul 13;20(1):653. doi: 10.1186/s12885-020-07143-2.
Results Reference
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Pyrotinib Combined With Trastuzumab and AI in the First-line Treatment of HER2 Positive/ HR Positive MBC
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