- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04900311
Pyrotinib Versus Pertuzumab in Combination With Neoadjuvant Trastuzumab and Nab-Paclitaxel in HER2+ Early or Locally Advanced Breast Cancer (Pyramid)
May 19, 2021 updated by: Tianjin Medical University Cancer Institute and Hospital
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.
Study Overview
Status
Not yet recruiting
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
490
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Jin Zhang, MD, Professor
- Phone Number: 2121 0086-22-23340123
- Email: zhangjin@tjmuch.com
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: pyrotinib + trastuzumab + nab-paclitaxel
|
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)
|
Active Comparator: pertuzumab + trastuzumab + nab-paclitaxel
|
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)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
tpCR (totally pathological Complete Response) assessed by the IRC(Independent Review Committee)
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).
|
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.
|
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 Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
iDFS (Invasive disease-free survival)
Time Frame: from the date of surgery till two years after study-defined treatment.
|
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:
|
from the date of surgery till two years after study-defined treatment.
|
EFS (event free survival)
Time Frame: from the date of surgery till two years after study-defined treatment.
|
EFS, defined as time from randomization to the first documentation of one of the following events:
|
from the date of surgery till two years after study-defined treatment.
|
ORR (Objective Response Rate)
Time Frame: At the end of neoadjuvant therapy (four cycles, 21 days per cycle).
|
the proportion of patients who achieved Complete Response (CR) or Partial Response (PR) during Cycles 1-4, according to RECIST v1.1
|
At the end of neoadjuvant therapy (four cycles, 21 days per cycle).
|
the rate of adopting 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).
|
the proportion of patients who have undergone breast-conserving surgery
|
evaluated right after surgery, which will be performed within 14 days after the completion neoadjuvant therapy (four cycles, 21 days per cycle).
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of serious adverse events and other adverse events of special interest
Time Frame: through study completion, an average of 2.5 years.
|
Assess the incidence of serious adverse events (SAEs) and other adverse events.
|
through study completion, an average of 2.5 years.
|
Exploratory biomarker analyses
Time Frame: through study completion, an average of 2.5 years.
|
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.
|
through study completion, an average of 2.5 years.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
May 1, 2021
Primary Completion (Anticipated)
December 1, 2023
Study Completion (Anticipated)
December 1, 2025
Study Registration Dates
First Submitted
April 28, 2021
First Submitted That Met QC Criteria
May 19, 2021
First Posted (Actual)
May 25, 2021
Study Record Updates
Last Update Posted (Actual)
May 25, 2021
Last Update Submitted That Met QC Criteria
May 19, 2021
Last Verified
April 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Paclitaxel
- Trastuzumab
- Albumin-Bound Paclitaxel
- Pertuzumab
Other Study ID Numbers
- MA-BC-II-020
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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