Back to resultsPyrotinib Versus Pertuzumab in Combination With Neoadjuvant Trastuzumab and Nab-Paclitaxel in HER2+ Early or Locally Advanced Breast Cancer (Pyramid)
Primary Purpose
HER2+ Early or Locally Advanced Breast Cancer
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
pyrotinib + trastuzumab + nab-paclitaxel
pertuzumab + trastuzumab + nab-paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for HER2+ Early or Locally Advanced Breast Cancer focused on measuring HER2+ breast cancer, neoadjuvant, pyrotinib
Eligibility Criteria
Inclusion Criteria:
- female patients, treatment-naïve, aged ≥ 18 years and ≤ 75 years;
- ECOG score 0-1 (ECOG, Eastern Cooperative Oncology Group);
- Histologically confirmed invasive breast cancer (early stage or locally advanced) :Primary tumor greater than 2 cm diameter and cT2-cT4/cN0-cN3/cM0 (clinical stage II and III);
- HER2 expression positive breast cancer confirmed by pathological examination,
- known hormone receptor status (ER and PR);
- the level of major organ function must meet the following requirements: blood routine test: neutrophil (ANC) ≥ 1.5 × 109/L; platelet count (PLT) ≥ 90 × 109/L; hemoglobin (Hb) ≥ 90g/L; blood biochemistry test: total bilirubin (TBIL) ≤ 2.5 × ULN (upper normal limit); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; echocardiography: LVEF ((Left Ventricular Ejection Fraction) ≥ 55%; 12 ECG: QT interval corrected by Fridericia method (QTcF) < 470 ms in women
- Female subjects who have not yet experienced menopausal or not surgically sterile agree to practice abstinence or use effective methods of contraception for at least 7 months during and after the last dose of study drug;
- Sign the informed consent form and are willing to cooperate in the follow-up.
Exclusion Criteria:
- breast cancer of both sides, stage IV breast cancer or metastatic breast cancer;
- inflammatory breast cancer;
- History of other malignancy, or previous anti-cancer therapy or radiotherapy for any malignancy, excluding cured carcinoma in situ of the cervix or squamous or basal cell carcinoma.
- simultaneously participated in other clinical trials;
- Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the patient has not fully recovered
- blood transfusion, or received colony-stimulating factor treatments before randomization;
- known history of allergy to any of the study medications and any of the ingredients or excipients of these medications;
- history of immunodeficiency, including positive HIV test, or suffering from other acquired, congenital immunodeficiency diseases, or history of organ transplantation.
- had any heart disease, including: (1) angina pectoris; (2) arrhythmia that is clinically significant or required medication; (3) myocardial infarction; (4) heart failure; (5) any other heart disease judged by the investigator as not suitable for this trial.
- pregnant or lactating
- Other concurrent serious diseases that are serious hazards to the patient's safety or may interfere with planned treatment (including but not limited to hypertension, severe diabetes, active infection, thyroid disease, etc.) ;
- Inability to swallow, chronic diarrhea, bowel obstruction, and other factors affecting medication intake and absorption.
- Any other condition that, in the opinion of the investigator, makes the subject unsuitable for this study.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
pyrotinib + trastuzumab + nab-paclitaxel
pertuzumab + trastuzumab + nab-paclitaxel
Arm Description
Outcomes
Primary Outcome Measures
tpCR (totally pathological Complete Response) assessed by the IRC(Independent Review Committee)
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 following completion of neoadjuvant therapy and surgery.
Secondary Outcome Measures
iDFS (Invasive disease-free survival)
iDFS, defined as the time from the first date of no disease (i.e., date of surgery) to the first documentation of one of the following events:
Disease recurrence (local, regional, distant, or contralateral) after surgery
Death from any cause
EFS (event free survival)
EFS, defined as time from randomization to the first documentation of one of the following events:
Disease progression (before surgery), as determined by the investigator using RECIST v1.1 Any evidence of in situ contralateral disease will not be identified as progressive disease (PD). Any evidence of invasive contralateral disease will be considered disease progression
Disease recurrence (local, regional, distant, or contralateral) after surgery
Death from any cause
ORR (Objective Response Rate)
the proportion of patients who achieved Complete Response (CR) or Partial Response (PR) during Cycles 1-4, according to RECIST v1.1
the rate of adopting breast-conserving surgery
the proportion of patients who have undergone breast-conserving surgery
Full Information
NCT ID
NCT04900311
First Posted
April 28, 2021
Last Updated
May 19, 2021
Sponsor
Tianjin Medical University Cancer Institute and Hospital
Collaborators
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
1. Study Identification
Unique Protocol Identification Number
NCT04900311
Brief Title
Pyrotinib Versus Pertuzumab in Combination With Neoadjuvant Trastuzumab and Nab-Paclitaxel in HER2+ Early or Locally Advanced Breast Cancer
Acronym
Pyramid
Official Title
Pyrotinib Versus Pertuzumab in Combination With Neoadjuvant Trastuzumab and Nab-Paclitaxel in HER2+ Early or Locally Advanced Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 2021 (Anticipated)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tianjin Medical University Cancer Institute and Hospital
Collaborators
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study is being conducted to evaluate the efficacy, and safety of pyrotinib versus pertuzumab in combination with trastuzumab and nab-paclitaxel for neoadjuvant treatment in HER2+ early or locally advanced breast cancer patients. To explore whether pyrotinib regimen could provide better clinical results compared with pertuzumab in the study population.
Detailed Description
This study is a multi-center, randomized, open-label, controlled trial. Eligible patients will be randomized to neoadjuvant pyrotinib or pertuzumab containing regimen every 3 weeks for four cycles before surgery. Randomization was stratified by the following factors: hormone receptor status and primary tumor size. After completing four cycles of neoadjuvant treatment, all patients who are eligible for surgery will undergo surgery and have their pathologic response evaluated. Following surgery, patients will receive 90-100 mg/m2 epirubicin and 600 mg/m2 cyclophosphamide every 3 weeks for 4 cycles. Clinicians will select subsequent treatments for patients based on guidelines as well as clinical practice at each site.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2+ Early or Locally Advanced Breast Cancer
Keywords
HER2+ breast cancer, neoadjuvant, pyrotinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
490 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
pyrotinib + trastuzumab + nab-paclitaxel
Arm Type
Experimental
Arm Title
pertuzumab + trastuzumab + nab-paclitaxel
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
pyrotinib + trastuzumab + nab-paclitaxel
Intervention Description
patients will be treated every 3 weeks for four cycles prior to surgery at following doses: pyrotinib: 400 mg/day, orally, qd trastuzumab: IV infusion on Day 1 every 3 weeks with loading dose of 8 mg/kg in Cycle 1, and 6 mg/kg in Cycles 2-4 nab-paclitaxel: 260 mg/m2 IV infusion on Day 1 every 3 weeks, or 125 mg/m2 IV infusion on Days 1, 8 and 15 every 3 weeks (the nab-paclitaxel administration cycle was determined by investigator at each site)
Intervention Type
Drug
Intervention Name(s)
pertuzumab + trastuzumab + nab-paclitaxel
Intervention Description
patients will be treated every 3 weeks for four cycles prior to surgery at following doses: pertuzumab: IV infusion on Day 1 every 3 weeks with loading dose of 840 mg for Cycle 1, followed by 420 mg for Cycles 2-4 trastuzumab: IV infusion on Day 1 every 3 weeks with loading dose of 8 mg/kg in Cycle 1, and 6 mg/kg in Cycles 2-4 nab-paclitaxel: 260 mg/m2 IV infusion on Day 1 every 3 weeks, or 125 mg/m2 IV infusion on Days 1, 8 and 15 every 3 weeks (the nab-paclitaxel administration cycle was determined by investigator at each site)
Primary Outcome Measure Information:
Title
tpCR (totally pathological Complete Response) assessed by the IRC(Independent Review Committee)
Description
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 following completion of neoadjuvant therapy and surgery.
Time Frame
Pathologic response will be evaluated right after surgery, which will be performed within 14 days after the completion neoadjuvant therapy (four cycles, 21 days per cycle).
Secondary Outcome Measure Information:
Title
iDFS (Invasive disease-free survival)
Description
iDFS, defined as the time from the first date of no disease (i.e., date of surgery) to the first documentation of one of the following events:
Disease recurrence (local, regional, distant, or contralateral) after surgery
Death from any cause
Time Frame
from the date of surgery till two years after study-defined treatment.
Title
EFS (event free survival)
Description
EFS, defined as time from randomization to the first documentation of one of the following events:
Disease progression (before surgery), as determined by the investigator using RECIST v1.1 Any evidence of in situ contralateral disease will not be identified as progressive disease (PD). Any evidence of invasive contralateral disease will be considered disease progression
Disease recurrence (local, regional, distant, or contralateral) after surgery
Death from any cause
Time Frame
from the date of surgery till two years after study-defined treatment.
Title
ORR (Objective Response Rate)
Description
the proportion of patients who achieved Complete Response (CR) or Partial Response (PR) during Cycles 1-4, according to RECIST v1.1
Time Frame
At the end of neoadjuvant therapy (four cycles, 21 days per cycle).
Title
the rate of adopting breast-conserving surgery
Description
the proportion of patients who have undergone breast-conserving surgery
Time Frame
evaluated right after surgery, which will be performed within 14 days after the completion neoadjuvant therapy (four cycles, 21 days per cycle).
Other Pre-specified Outcome Measures:
Title
Incidence of serious adverse events and other adverse events of special interest
Description
Assess the incidence of serious adverse events (SAEs) and other adverse events.
Time Frame
through study completion, an average of 2.5 years.
Title
Exploratory biomarker analyses
Description
The correlation between baseline molecular biomarkers and efficacy outcomes will be evaluated. Biomarkers may include blood lipids and metabolomics profiles based on Nuclear Magnetic Resonance techniques.
Time Frame
through study completion, an average of 2.5 years.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
female patients, treatment-naïve, aged ≥ 18 years and ≤ 75 years;
ECOG score 0-1 (ECOG, Eastern Cooperative Oncology Group);
Histologically confirmed invasive breast cancer (early stage or locally advanced) :Primary tumor greater than 2 cm diameter and cT2-cT4/cN0-cN3/cM0 (clinical stage II and III);
HER2 expression positive breast cancer confirmed by pathological examination,
known hormone receptor status (ER and PR);
the level of major organ function must meet the following requirements: blood routine test: neutrophil (ANC) ≥ 1.5 × 109/L; platelet count (PLT) ≥ 90 × 109/L; hemoglobin (Hb) ≥ 90g/L; blood biochemistry test: total bilirubin (TBIL) ≤ 2.5 × ULN (upper normal limit); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; echocardiography: LVEF ((Left Ventricular Ejection Fraction) ≥ 55%; 12 ECG: QT interval corrected by Fridericia method (QTcF) < 470 ms in women
Female subjects who have not yet experienced menopausal or not surgically sterile agree to practice abstinence or use effective methods of contraception for at least 7 months during and after the last dose of study drug;
Sign the informed consent form and are willing to cooperate in the follow-up.
Exclusion Criteria:
breast cancer of both sides, stage IV breast cancer or metastatic breast cancer;
inflammatory breast cancer;
History of other malignancy, or previous anti-cancer therapy or radiotherapy for any malignancy, excluding cured carcinoma in situ of the cervix or squamous or basal cell carcinoma.
simultaneously participated in other clinical trials;
Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the patient has not fully recovered
blood transfusion, or received colony-stimulating factor treatments before randomization;
known history of allergy to any of the study medications and any of the ingredients or excipients of these medications;
history of immunodeficiency, including positive HIV test, or suffering from other acquired, congenital immunodeficiency diseases, or history of organ transplantation.
had any heart disease, including: (1) angina pectoris; (2) arrhythmia that is clinically significant or required medication; (3) myocardial infarction; (4) heart failure; (5) any other heart disease judged by the investigator as not suitable for this trial.
pregnant or lactating
Other concurrent serious diseases that are serious hazards to the patient's safety or may interfere with planned treatment (including but not limited to hypertension, severe diabetes, active infection, thyroid disease, etc.) ;
Inability to swallow, chronic diarrhea, bowel obstruction, and other factors affecting medication intake and absorption.
Any other condition that, in the opinion of the investigator, makes the subject unsuitable for this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jin Zhang, MD, Professor
Phone
0086-22-23340123
Ext
2121
Email
zhangjin@tjmuch.com
12. IPD Sharing Statement
Learn more about this trial
Pyrotinib Versus Pertuzumab in Combination With Neoadjuvant Trastuzumab and Nab-Paclitaxel in HER2+ Early or Locally Advanced Breast Cancer
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