search
Back to results

Pyrotinib Combined With Trastuzumab,Dalpiciclib and Letrozole for HR+/HER2+ Breast Cancer

Primary Purpose

Breast Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
pyrotinib combined with trastuzumab, dalpiciclib and letrozole
Sponsored by
Yantai Yuhuangding Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring breast cancer; CDK4/6 inhibitor; hormone receptor-positive; HER2 positive; dalpiciclib; pyrotinib ;

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: A ECOG PS score of 0-1; Postmenopausal or pre menopausal/perimenopausal women aged ≥ 18 years who must receive LHRH agonists during the study period; Pathological examination confirmed invasive breast cancer with positive ER, PR and HER 2; (1)Follow the 2018 ASCO-CAP HER 2 positive interpretation guidelines. The pathology laboratory confirms that the immunohistochemical (IHC) score is 3+, or 2+and the in situ hybridization (ISH) test is positive; (2)ER positive was defined as the percentage of ER positive cells ≥ 10%; (3)The percentage of PR positive cells ≥ 10%; 4、The tumor stage is early (T2-3, N0-1, M0) or locally advanced (T2-3, N2-3, M0) patients with breast cancer newly treated; 5、The functions of main organs meet the following requirements (no blood transfusion, no use of whitening and platelet raising drugs within 2 weeks before screening): Blood routine examination: neutrophil (ANC) ≥ 1.5 × 109/L; Platelet count (PLT) ≥ 90 × 109/L; Hemoglobin (Hb) ≥ 90g/L; Blood biochemistry: total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; Alkaline phosphatase ≤ 2.5 × ULN; Urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; Color Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥ 55%; (4)12 lead ECG: Fridericia corrected QT interval (QTcF)<470 msec. 6、Women who can accept biopsy; 7、Volunteered to participate in this study; signed informed consent; with good compliance and willingness to follow-up. Exclusion Criteria: Patients with stage IV breast cancer; Inflammatory breast cancer; Previous antineoplastic treatment or radiotherapy for any malignant tumor, excluding cured cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinoma; At the same time, he received anti-tumor therapy in other clinical trials, including endocrine therapy, bisphosphonate therapy or immunotherapy; The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not completely recovered from such surgical procedures; Serious heart disease or discomfort, including but not limited to the following diseases: (1)History of diagnosis of heart failure or systolic dysfunction (LVEF<50%); (2)High risk uncontrolled arrhythmia, such as atrial tachycardia, resting heart rate>100 bpm, significant ventricular arrhythmia (such as ventricular tachycardia) or higher grade atrioventricular block (i.e. Mobitz Ⅱ second degree atrioventricular block or third degree atrioventricular block); (3)Angina pectoris requiring anti angina drugs; (4)Valvular heart disease with clinical significance; (5)ECG showed transmural myocardial infarction; (6)Poor control of hypertension (systolic blood pressure>180mmHg and/or diastolic blood pressure>100mmHg); 7、Inability to swallow, intestinal obstruction or other factors affecting drug administration and absorption; 8、People known to have a history of allergy to the drug components of this protocol; 9、Have a history of immunodeficiency, including HIV test positive, or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 10、Female patients during pregnancy and lactation, female patients with fertility and positive baseline pregnancy test, or patients of childbearing age who are unwilling to take effective contraceptive measures during the whole trial period and within 7 months after the last study drug use; 11、Those who have a history of abuse of psychotropic substances and cannot quit or have mental disorders; 12、Suffering from serious concomitant diseases or other conditions that may interfere with the planned treatment of concomitant diseases, or any other conditions that the investigator believes are not suitable for the patient to participate in this study.

Sites / Locations

  • Yantai Yuhuangding HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

cohort 1

Arm Description

patients with stage II-III HR+/HER2+ breast cancer

Outcomes

Primary Outcome Measures

pathologic complete response
After neoadjuvant therapy, there are no residual invasive tumors in the primary focus and regional lymph nodes of breast cancer, but ductal carcinoma in situ may be present(ypT0/is ypN0)

Secondary Outcome Measures

objective response rate
The rate of CR and PR,determined using RECIST v1.1 criteria
breast-conserving surgery rate
The number of cases that actually underwent breast-conserving surgery after surgery accounted for the percentage of all breast cancer patients who underwent surgery
safety profile
Adverse events (AE) and severe adverse events (SAEs) are recorded. Refer to NCI-CTC AE 5.0 standard

Full Information

First Posted
March 23, 2023
Last Updated
March 23, 2023
Sponsor
Yantai Yuhuangding Hospital
Collaborators
Jiangsu Hengrui Pharmaceutical Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT05800756
Brief Title
Pyrotinib Combined With Trastuzumab,Dalpiciclib and Letrozole for HR+/HER2+ Breast Cancer
Official Title
Pyrotinib Combined With Trastuzumab, Dalpiciclibe and Letrozole for HR+/HER2+ Breast Cancer:A Single Arm, Open Label, Phase II Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 4, 2022 (Actual)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
July 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yantai Yuhuangding Hospital
Collaborators
Jiangsu Hengrui Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
In this single arm, open label, phase 2 trial, operable patients with stage II-III HR+/HER2+ breast cancer will be enrolled and receive two cycles of pyrotinib combined with trastuzumab, dalpiciclib and letrozole. Imaging evaluation was performed two weeks later, and patients who achieved CR or PR were continued with the original regimen for 4 cycles. Subjects who did not achieve PR switched to regimen and received 4 cycles of pyrotinib combined with trastuzumab plus chemotherapy. This study aims to assessed the biological effects and safety of pyrotinib combined with trastuzumab, dalpiciclib and letrozole for HR+/HER2+ breast cancer in the neoadjuvant setting.
Detailed Description
This is a single arm, open label, phase 2 trial aimed to investigate the biological effects and safety of pyrotinib combined with trastuzumab, dalpiciclib and letrozole for HR+/HER2+ breast cancer. A total of 30 patients with stage II-III HR+/HER2+ breast cancer will be enrolled. Subjects will be enrolled and receive two cycles of pyrotinib combined with trastuzumab, dalpiciclib and letrozole. Imaging evaluation was performed two weeks later, and patients who achieved CR or PR were continued with the original regimen for 4 cycles. Subjects who did not achieve PR switched to regimen and received 4 cycles of pyrotinib combined with trastuzumab plus chemotherapy. In a specific medication cycle, patients use dalpiciclib orally, 125mg, day 1-21, and letrozole orally, 2.5 mg, day 1-28, and pyrotinib orally, 320mg, day 1-28, and trastuzumab, injection, 8 mg/kg loading dose in cycle 1, 6mg/kg in cycles 2-6, intravenous drops, 1 cycle on day 1-21. Premenopausal or perimenopausal patients should combine ovarian function suppression, including bilateral oophorectomy or treatment with gonadotropin-releasing hormone agonists. The primary endpoint is pathological complete response rate. The secondary endpoints include overall response rate, breast-conserving surgery rate and safety profile.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
breast cancer; CDK4/6 inhibitor; hormone receptor-positive; HER2 positive; dalpiciclib; pyrotinib ;

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
cohort 1
Arm Type
Experimental
Arm Description
patients with stage II-III HR+/HER2+ breast cancer
Intervention Type
Drug
Intervention Name(s)
pyrotinib combined with trastuzumab, dalpiciclib and letrozole
Intervention Description
Six 4-week cycles of dalpiciclib orally, 125mg, day 1-21, and letrozole orally, 2.5 mg, day 1-28, and pyrotinib orally, 320mg, day 1-28, and trastuzumab, injection, 8 mg/kg loading dose in cycle 1, 6mg/kg in cycles 2-6, intravenous drops, 1 cycle on day 1-21.
Primary Outcome Measure Information:
Title
pathologic complete response
Description
After neoadjuvant therapy, there are no residual invasive tumors in the primary focus and regional lymph nodes of breast cancer, but ductal carcinoma in situ may be present(ypT0/is ypN0)
Time Frame
up 2 years
Secondary Outcome Measure Information:
Title
objective response rate
Description
The rate of CR and PR,determined using RECIST v1.1 criteria
Time Frame
up 2 years
Title
breast-conserving surgery rate
Description
The number of cases that actually underwent breast-conserving surgery after surgery accounted for the percentage of all breast cancer patients who underwent surgery
Time Frame
up 2 years
Title
safety profile
Description
Adverse events (AE) and severe adverse events (SAEs) are recorded. Refer to NCI-CTC AE 5.0 standard
Time Frame
up 2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A ECOG PS score of 0-1; Postmenopausal or pre menopausal/perimenopausal women aged ≥ 18 years who must receive LHRH agonists during the study period; Pathological examination confirmed invasive breast cancer with positive ER, PR and HER 2; (1)Follow the 2018 ASCO-CAP HER 2 positive interpretation guidelines. The pathology laboratory confirms that the immunohistochemical (IHC) score is 3+, or 2+and the in situ hybridization (ISH) test is positive; (2)ER positive was defined as the percentage of ER positive cells ≥ 10%; (3)The percentage of PR positive cells ≥ 10%; 4、The tumor stage is early (T2-3, N0-1, M0) or locally advanced (T2-3, N2-3, M0) patients with breast cancer newly treated; 5、The functions of main organs meet the following requirements (no blood transfusion, no use of whitening and platelet raising drugs within 2 weeks before screening): Blood routine examination: neutrophil (ANC) ≥ 1.5 × 109/L; Platelet count (PLT) ≥ 90 × 109/L; Hemoglobin (Hb) ≥ 90g/L; Blood biochemistry: total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; Alkaline phosphatase ≤ 2.5 × ULN; Urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; Color Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥ 55%; (4)12 lead ECG: Fridericia corrected QT interval (QTcF)<470 msec. 6、Women who can accept biopsy; 7、Volunteered to participate in this study; signed informed consent; with good compliance and willingness to follow-up. Exclusion Criteria: Patients with stage IV breast cancer; Inflammatory breast cancer; Previous antineoplastic treatment or radiotherapy for any malignant tumor, excluding cured cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinoma; At the same time, he received anti-tumor therapy in other clinical trials, including endocrine therapy, bisphosphonate therapy or immunotherapy; The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not completely recovered from such surgical procedures; Serious heart disease or discomfort, including but not limited to the following diseases: (1)History of diagnosis of heart failure or systolic dysfunction (LVEF<50%); (2)High risk uncontrolled arrhythmia, such as atrial tachycardia, resting heart rate>100 bpm, significant ventricular arrhythmia (such as ventricular tachycardia) or higher grade atrioventricular block (i.e. Mobitz Ⅱ second degree atrioventricular block or third degree atrioventricular block); (3)Angina pectoris requiring anti angina drugs; (4)Valvular heart disease with clinical significance; (5)ECG showed transmural myocardial infarction; (6)Poor control of hypertension (systolic blood pressure>180mmHg and/or diastolic blood pressure>100mmHg); 7、Inability to swallow, intestinal obstruction or other factors affecting drug administration and absorption; 8、People known to have a history of allergy to the drug components of this protocol; 9、Have a history of immunodeficiency, including HIV test positive, or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 10、Female patients during pregnancy and lactation, female patients with fertility and positive baseline pregnancy test, or patients of childbearing age who are unwilling to take effective contraceptive measures during the whole trial period and within 7 months after the last study drug use; 11、Those who have a history of abuse of psychotropic substances and cannot quit or have mental disorders; 12、Suffering from serious concomitant diseases or other conditions that may interfere with the planned treatment of concomitant diseases, or any other conditions that the investigator believes are not suitable for the patient to participate in this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yizi Cong
Phone
86-0535-6024603
Email
congyizi@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guangdong Qiao
Organizational Affiliation
Yantai Yuhuangding Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yantai Yuhuangding Hospital
City
Yantai
State/Province
Shandong
ZIP/Postal Code
264000
Country
China
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

Pyrotinib Combined With Trastuzumab,Dalpiciclib and Letrozole for HR+/HER2+ Breast Cancer

We'll reach out to this number within 24 hrs