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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
490

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: pyrotinib + trastuzumab + nab-paclitaxel
Drug: 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
Drug: 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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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:

  1. Disease recurrence (local, regional, distant, or contralateral) after surgery
  2. Death from any cause
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:

  1. 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
  2. Disease recurrence (local, regional, distant, or contralateral) after surgery
  3. Death from any cause
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tianjin Medical University Cancer Institute and Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 28, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 25, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 25, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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