Back to resultsPyrotinib or Trastuzumab Plus Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer
Primary Purpose
Breast Cancer
Status
Terminated
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Pyrotinib
nab-Paclitaxel
Trastuzumab
EC chemotherapy
Surgery
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring HER2-positive, neoadjuvant
Eligibility Criteria
Inclusion Criteria:
- With signed consent
- Histologically confirmed invasive breast carcinoma with a primary tumor size of no less than (≥) 2 centimeters (cm) by standard local assessment technique
- Breast cancer stage at presentation: stage I-III
- HER2-positive breast cancer defined as 3+ score by immunohistochemistry in > 10 percent (%) of immunoreactive cells or HER2 gene amplification by in situ hybridization
- Known hormone receptor status (estrogen receptor and/or progesterone receptor)
- Eastern Cooperative Oncology Group Performance Status equal to or less than (<=) 1
- Baseline left ventricular ejection fracture >= 50% measured by echocardiography
- Willing to use highly effective form of nonhormonal contraception while on study and for 7 months after end of study treatment for female with fertility or male
- Negative serum pregnancy test for women with fertility
- Willing to obey the study protocol
Exclusion Criteria:
- Stage IV disease
- Previous anti-cancer therapy or radiotherapy for any malignancy
- History of other malignancy within 5 years prior to screening, except for appropriately-treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
- Concurrent anti-cancer treatment in another investigational trial, including hormone therapy, bisphosphonate therapy, or immunotherapy
- Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the participant has not fully recovered
- Serious cardiac illness or medical condition
- Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
- Any abnormalities in liver, kidney or hematologic function laboratory tests immediately prior to randomization
- Sensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol
- Not able to swallow the drug
- Pregnant or lactating
Sites / Locations
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Pyrotinib in combination with nab-paclitaxel
Trastuzumab in combination with nab-paclitaxel
Arm Description
Prior to surgery: pyrotinib and nab-paclitaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with epirubicin and cyclophosphamide (EC): trastuzumab up to 1 year total.
Prior to surgery: trastuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with epirubicin and cyclophosphamide (EC): trastuzumab up to 1 year total.
Outcomes
Primary Outcome Measures
Percentage of Participants With Total Pathologic Complete Response (tpCR)
tpCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer [AJCC] staging system).The duration of one treatment cycle is 21 days.
Secondary Outcome Measures
Percentage of Participants With Breast Pathologic Complete Response (bpCR)
bpCR is defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is, in accordance with current AJCC staging system).The duration of one treatment cycle is 21 days.
Clinical response
Percentage of Participants With Complete Response, Partial Response, Stable Disease, or Progressive Disease During Cycles 1-4, According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The duration of one treatment cycle is 21 days.
Event-free survival (EFS)
EFS is defined as the time from randomization to the first documentation of one of the following events: Disease progression (before surgery) as determined by the investigator with use of RECIST v1.1 Any evidence of contralateral disease in situ was not identified as progressive disease; Disease recurrence (local, regional, distant, or contralateral) after surgery; Death from any cause.
Disease-free survival (DFS)
DFS was defined as the time from first date of no disease (i.e., date of surgery) to first documentation of one of the following events: Disease recurrence (local, regional, distant, or contralateral) after surgery. Any evidence of contralateral disease in situ was not identified as disease recurrence; Death from any cause.
Overall survival (OS)
OS was defined as the time from randomization to death from any cause.
Full Information
NCT ID
NCT04066790
First Posted
August 19, 2019
Last Updated
May 16, 2020
Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Jiangsu HengRui Medicine Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04066790
Brief Title
Pyrotinib or Trastuzumab Plus Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer
Official Title
A Randomised, Multicenter, Open-label, Phase II Study Evaluating Pyrotinib or Trastuzumab Plus Nab-paclitaxel as Neoadjuvant Therapy in Early Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2 - Positive Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Terminated
Why Stopped
We terminated this trial and initiated a new one including pertuzumab.
Study Start Date
September 9, 2019 (Actual)
Primary Completion Date
April 30, 2020 (Actual)
Study Completion Date
April 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Jiao Tong University School of Medicine
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
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study aims to evaluate the efficacy and safety of pyrotinib in combination with nab-paclitaxel or trastuzumab with nab-paclitaxel as neoadjuvant therapy in early stage or locally advanced HER2-positive breast cancer.
Detailed Description
The study evaluate the pathological complete response rate, event-free survival, disease-free survival, overall survival and safety of pyrotinib in combination with nab-paclitaxel or trastuzumab with nab-paclitaxel as neoadjuvant therapy in early stage or locally advanced HER2-positive breast cancer. Patients will receive 4 cycles of pyrotinib in combination with nab-paclitaxel or 4 cycles of trastuzumab with nab-paclitaxel as neoadjuvant therapy, then undergo surgery, then receive 4 cycles of epirubicin in combination with cyclophosphamide, then complete 1 year of trastuzumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
HER2-positive, neoadjuvant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pyrotinib in combination with nab-paclitaxel
Arm Type
Experimental
Arm Description
Prior to surgery: pyrotinib and nab-paclitaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with epirubicin and cyclophosphamide (EC): trastuzumab up to 1 year total.
Arm Title
Trastuzumab in combination with nab-paclitaxel
Arm Type
Active Comparator
Arm Description
Prior to surgery: trastuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with epirubicin and cyclophosphamide (EC): trastuzumab up to 1 year total.
Intervention Type
Drug
Intervention Name(s)
Pyrotinib
Intervention Description
Pyrotinib 400 mg taken orally everyday, every 3 weeks, for 4 cycles.
Intervention Type
Drug
Intervention Name(s)
nab-Paclitaxel
Intervention Description
Nab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Intervention Description
Trastuzumab IV infusion in 3-week cycles. Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4. Adjuvant treatment: 8 mg/kg loading dose for Cycle 9, followed by 6 mg/kg for remaining cycles till completion of 1 year trastuzumab
Intervention Type
Drug
Intervention Name(s)
EC chemotherapy
Intervention Description
epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks 4 cycles (Cycles 5-8)
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.
Primary Outcome Measure Information:
Title
Percentage of Participants With Total Pathologic Complete Response (tpCR)
Description
tpCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer [AJCC] staging system).The duration of one treatment cycle is 21 days.
Time Frame
Cycle 4 . The duration of one treatment cycle is 21 days.
Secondary Outcome Measure Information:
Title
Percentage of Participants With Breast Pathologic Complete Response (bpCR)
Description
bpCR is defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is, in accordance with current AJCC staging system).The duration of one treatment cycle is 21 days.
Time Frame
Cycle 4 . The duration of one treatment cycle is 21 days.
Title
Clinical response
Description
Percentage of Participants With Complete Response, Partial Response, Stable Disease, or Progressive Disease During Cycles 1-4, According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The duration of one treatment cycle is 21 days.
Time Frame
Cycle 4 . The duration of one treatment cycle is 21 days.
Title
Event-free survival (EFS)
Description
EFS is defined as the time from randomization to the first documentation of one of the following events: Disease progression (before surgery) as determined by the investigator with use of RECIST v1.1 Any evidence of contralateral disease in situ was not identified as progressive disease; Disease recurrence (local, regional, distant, or contralateral) after surgery; Death from any cause.
Time Frame
From Baseline to EFS event or date last known to be alive and event-free (up to 5 years)
Title
Disease-free survival (DFS)
Description
DFS was defined as the time from first date of no disease (i.e., date of surgery) to first documentation of one of the following events: Disease recurrence (local, regional, distant, or contralateral) after surgery. Any evidence of contralateral disease in situ was not identified as disease recurrence; Death from any cause.
Time Frame
From surgery to DFS event or date last known to be alive and event-free (up to 5 years)
Title
Overall survival (OS)
Description
OS was defined as the time from randomization to death from any cause.
Time Frame
From Baseline to OS event or date last known to be alive (up to 5 years)
Other Pre-specified Outcome Measures:
Title
Percentage of Participants With At Least One Adverse Event During Treatment Period
Description
The percentage of participants who experienced at least one adverse event during the neoadjuvant period, surgery, adjuvant treatment period.
Time Frame
From randomization to 30 days after completion of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
With signed consent
Histologically confirmed invasive breast carcinoma with a primary tumor size of no less than (≥) 2 centimeters (cm) by standard local assessment technique
Breast cancer stage at presentation: stage I-III
HER2-positive breast cancer defined as 3+ score by immunohistochemistry in > 10 percent (%) of immunoreactive cells or HER2 gene amplification by in situ hybridization
Known hormone receptor status (estrogen receptor and/or progesterone receptor)
Eastern Cooperative Oncology Group Performance Status equal to or less than (<=) 1
Baseline left ventricular ejection fracture >= 50% measured by echocardiography
Willing to use highly effective form of nonhormonal contraception while on study and for 7 months after end of study treatment for female with fertility or male
Negative serum pregnancy test for women with fertility
Willing to obey the study protocol
Exclusion Criteria:
Stage IV disease
Previous anti-cancer therapy or radiotherapy for any malignancy
History of other malignancy within 5 years prior to screening, except for appropriately-treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
Concurrent anti-cancer treatment in another investigational trial, including hormone therapy, bisphosphonate therapy, or immunotherapy
Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the participant has not fully recovered
Serious cardiac illness or medical condition
Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
Any abnormalities in liver, kidney or hematologic function laboratory tests immediately prior to randomization
Sensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol
Not able to swallow the drug
Pregnant or lactating
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kunwei Shen, MD
Organizational Affiliation
Ruijin Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Pyrotinib or Trastuzumab Plus Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer
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