Back to results

Clinical Study of Pyrotinib in Neoadjuvant Therapy of HR-positive and HER2-positive Breast Cancer

Primary Purpose

Breast Cancer

Status

Not yet recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Neoadjuvant therapy: TCbHPy

Neoadjuvant therapy: TCbHP

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring HR+/HER2+ Breast cancer, Neoadjuvant therapy, pyrotinib

Eligibility Criteria

20 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Women aged 18-70 with breast cancer;
Pathologically confirmed unilateral invasive ductal carcinoma (with or without intraductal carcinoma components);
Proposed to receive neoadjuvant therapy;
Positive ER and/or PgR (defined as ≥10% positive immunohistochemical test);
HER2 positive (defined as IMMUNOHISTOchemical HER2 ++, or HER2 ++ and in situ hybridization (ISH) results in HER2 gene amplification);
There is no evidence of metastasis in clinical or imaging;
ECOG score 0 or 1;
White blood cell count ≥3.5×109/L, neutrophil count ≥2×109/L, platelet count ≥100×109/L and hemoglobin ≥90 g/L before neoadjuvant therapy;
Before neoadjuvant therapy, AST and ALT < 1.5 times the upper limit of normal value, alkaline phosphatase < 2.5 times the upper limit of normal value, total bilirubin < 1.5 times the upper limit of normal value; Serum creatinine < 1.5 times the upper limit of normal value;
LVEF≥55% on 2d echocardiography before neoadjuvant therapy;
Signed informed consent.

Exclusion Criteria:

Clinical or imaging suspicion of lateral breast malignancy has not been confirmed;
Prior malignancy (except basal cell carcinoma of the skin and carcinoma in situ of the cervix), including contralateral breast cancer;
The patient has been enrolled in other clinical trials;
Patients suffering from serious systemic diseases and/or uncontrollable infections cannot be enrolled in the study;
Severe cardiovascular and cerebrovascular diseases (e.g., unstable angina pectoris, chronic heart failure, uncontrolled hypertension > 150/90mmHg, myocardial infarction or cerebrovascular accident) within the first 6 months of randomization;
Have a history of blood system diseases, especially platelet-related diseases;
Patients with previous intestinal inflammation, intestinal dysfunction, severe diarrhea and constipation;
People who are known to be allergic to chemotherapy drugs, targeted drugs or TKI drugs;
Women of childbearing age refuse contraception during treatment and within 8 weeks after completion of treatment;
Pregnant and lactation women;
positive pregnancy test before drug use after joining the test;
Mental illness, cognitive impairment, inability to understand the test protocol and side effects, inability to complete the test protocol and follow-up workers (systematic evaluation is required before the trial is enrolled);
Persons without personal freedom and independent capacity for civil conduct.

Sites / Locations

the First Affiliated Hospital of Nanjing Medical University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TCbHPy*6

TCbHP*6

Arm Description

Pyrotinib combined with docetaxel, carboplatin and trastuzumab for 6 cycles (Every three weeks). T (Docetaxel 100 mg/m2, d1) C (Carboplatin, AUC 6, D1) H (Trastuzumab, 8 mg/kg for the first dose, 6 mg/kg for the rest, D1) Py (pyrotinib 400mg, qD, D1-21)

Pertuzumab combined with docetaxel, carboplatin and trastuzumab for 6 cycles (Every three weeks). T (Docetaxel 100 mg/m2, d1) C (Carboplatin, AUC 6, D1) H (Trastuzumab, 8 mg/kg for the first dose, 6 mg/kg for the rest, D1) P (Pertuzumab, 840mg for the first dose, 420mg for the rest, D1))

Outcomes

Primary Outcome Measures

tpCR rate (ypT0/is ypN0)

Pathological complete response rate after neoadjuvant ( both breast and axillary lymph nodes, in which the breast may have residual carcinoma in situ)

Secondary Outcome Measures

iDFS

invasive Disease Free Survival

EFS

Event Free Survival

Full Information

NCT ID

NCT05430347

First Posted

June 12, 2022

Last Updated

February 19, 2023

Sponsor

The First Affiliated Hospital with Nanjing Medical University

1. Study Identification

Unique Protocol Identification Number

NCT05430347

Brief Title

Clinical Study of Pyrotinib in Neoadjuvant Therapy of HR-positive and HER2-positive Breast Cancer

Official Title

A Multicenter Phase II Clinical Study of Pyrotinib or Pertuzumab Combined With Docetaxel, Carboplatin, and Trastuzumab in Neoadjuvant Therapy for HR-positive, HER2-positive Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

April 15, 2023 (Anticipated)

Primary Completion Date

June 15, 2025 (Anticipated)

Study Completion Date

September 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The First Affiliated Hospital with Nanjing Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Due to neoadjuvant therapy with trastuzumab and pertuzumab is less effective for HR+/HER2+ breast cancer, and the PHEDRA Clinical Study subgroup analysis showed that the addition of pyrotinib to trastuzumab more than doubled pCR rates in HR+/HER2+ patients. our research group proposed a hypothesis that pyrotinib may be more advantageous for HR+/HER2+ breast cancer. Therefore, our center intends to carry out a multi-center, randomized controlled, prospective clinical study to compare the efficacy of pyrotinib or pertuzumab combined with docetaxel, carboplatin and trastuzumab in neoadjuvant therapy for patients with HR+/HER2+ breast cancer, and to conduct a comparative study on the safety.

Detailed Description

Different anti-HER2-targeting drugs act on different parts and types of HER2 molecules, so their mechanisms and effects are different. Trastuzumab and pertuzumab are the most commonly used anti-HER2 targeting drugs, which target the extracellular segment of THE HER2 molecule. The major guidelines recommend the use of trastuzumab and pertuzumab in the use of neoadjuvant therapy with a two-target regimen. Another commonly used class of anti-HER2-targeting drugs are Tyrosine kinase inhibitors (TKI), which target the intracellular segment of the HER2 molecule. Not only that, take domestically developed pyrotinib as an example, in addition to targeting HER2, it also targets HER1 and HER4. Because of the different mechanisms of action, TKI is still effective in patients with trastuzumab and/or pertuzumab resistant relapsing metastasis. To investigate the efficacy of pyrotinib in neoadjuvant therapy, a prospective, randomized, double-blind, multicenter clinical trial, the PHEDRA Clinical Study, was conducted in China. Results presented at the 2021 ASCO Meeting showed that addition of pyrotinib to trastuzumab also significantly increased tpCR rate (22.0% vs 41.0%; P < 0.0001), and the pCR rate was similar to trastuzumab + pertuzumab double target (39.3% for Neosphere and Peony). Based on these results, neoadjuvant therapy regimens with trastuzumab and TKI have been included in the 2022 CSCO guidelines. Of note, there were also differences in Hormone Receptor (HR) status in patients with HER2-positive breast cancer. After neoadjuvant chemotherapy combined with trastuzumab and pertuzumab double-target therapy, the pCR rate of HR-/HER2+ breast cancer was higher than HR+/HER2+ breast cancer. In contrast, a PHEDRA subgroup analysis showed that the addition of pyrotinib to trastuzumab more than doubled pCR rates in HR+/HER2+ patients (29.9% vs 12.2%) . In addition, in another adjunctive study of TKI drug neratinib, subgroup results also suggested that neratinib had a better effect on HR+/HER2+. Based on the above results, our research group proposed a hypothesis that TKI drugs may be more advantageous for HR+/HER2+ breast cancer. Therefore, our center intends to carry out a multi-center, randomized controlled, prospective clinical study to compare the efficacy of pyrotinib or pertuzumab combined with docetaxel, carboplatin and trastuzumab in neoadjuvant therapy for patients with HR+/HER2+ breast cancer, and to conduct a comparative study on the safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

HR+/HER2+ Breast cancer, Neoadjuvant therapy, pyrotinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

The treatment regimen of the experimental group was pyrotinib combined with docetaxel, carboplatin and trastuzumab, while the treatment regimen of the control group was pertuzumab combined with docetaxel, carboplatin and trastuzumab (the control group was standard treatment). Surgical treatment was performed after 6 courses of neoadjuvant therapy

Masking

None (Open Label)

Masking Description

This study is an open-design, multicenter, randomized controlled prospective clinical study with 80 patients. Subjects will be randomly assigned 1:1.

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

TCbHPy*6

Arm Type

Experimental

Arm Description

Arm Title

TCbHP*6

Arm Type

Active Comparator

Arm Description

Intervention Type

Combination Product

Intervention Name(s)

Neoadjuvant therapy: TCbHPy

Intervention Description

Pyrotinib combined with docetaxel, carboplatin and trastuzumab (TCbHPy) for neoadjuvant therapy of HR+/HER2+ breast cancer

Intervention Type

Combination Product

Intervention Name(s)

Neoadjuvant therapy: TCbHP

Intervention Description

Pertuzumab combined with docetaxel, carboplatin and trastuzumab (TCbHP) for neoadjuvant therapy of HR+/HER2+ breast cancer

Primary Outcome Measure Information:

Title

tpCR rate (ypT0/is ypN0)

Description

Pathological complete response rate after neoadjuvant ( both breast and axillary lymph nodes, in which the breast may have residual carcinoma in situ)

Time Frame

1 month after surgery

Secondary Outcome Measure Information:

Title

iDFS

Description

invasive Disease Free Survival

Time Frame

3 years

Title

EFS

Description

Event Free Survival

Time Frame

3 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Women aged 18-70 with breast cancer; Pathologically confirmed unilateral invasive ductal carcinoma (with or without intraductal carcinoma components); Proposed to receive neoadjuvant therapy; Positive ER and/or PgR (defined as ≥10% positive immunohistochemical test); HER2 positive (defined as IMMUNOHISTOchemical HER2 ++, or HER2 ++ and in situ hybridization (ISH) results in HER2 gene amplification); There is no evidence of metastasis in clinical or imaging; ECOG score 0 or 1; White blood cell count ≥3.5×109/L, neutrophil count ≥2×109/L, platelet count ≥100×109/L and hemoglobin ≥90 g/L before neoadjuvant therapy; Before neoadjuvant therapy, AST and ALT < 1.5 times the upper limit of normal value, alkaline phosphatase < 2.5 times the upper limit of normal value, total bilirubin < 1.5 times the upper limit of normal value; Serum creatinine < 1.5 times the upper limit of normal value; LVEF≥55% on 2d echocardiography before neoadjuvant therapy; Signed informed consent. Exclusion Criteria: Clinical or imaging suspicion of lateral breast malignancy has not been confirmed; Prior malignancy (except basal cell carcinoma of the skin and carcinoma in situ of the cervix), including contralateral breast cancer; The patient has been enrolled in other clinical trials; Patients suffering from serious systemic diseases and/or uncontrollable infections cannot be enrolled in the study; Severe cardiovascular and cerebrovascular diseases (e.g., unstable angina pectoris, chronic heart failure, uncontrolled hypertension > 150/90mmHg, myocardial infarction or cerebrovascular accident) within the first 6 months of randomization; Have a history of blood system diseases, especially platelet-related diseases; Patients with previous intestinal inflammation, intestinal dysfunction, severe diarrhea and constipation; People who are known to be allergic to chemotherapy drugs, targeted drugs or TKI drugs; Women of childbearing age refuse contraception during treatment and within 8 weeks after completion of treatment; Pregnant and lactation women; positive pregnancy test before drug use after joining the test; Mental illness, cognitive impairment, inability to understand the test protocol and side effects, inability to complete the test protocol and follow-up workers (systematic evaluation is required before the trial is enrolled); Persons without personal freedom and independent capacity for civil conduct.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jue Wang, Doctor

Phone

+86-18061695508

wangjue200011@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Rui Chen, Master

Phone

+86-15951756315

15951756315@163.com

Facility Information:

Facility Name

the First Affiliated Hospital of Nanjing Medical University

City

Nanjing

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Clinical Study of Pyrotinib in Neoadjuvant Therapy of HR-positive and HER2-positive Breast Cancer

We'll reach out to this number within 24 hrs