Pyrotinib Combined With Trastuzumab, Dalpiciclib, Letrozole Versus TCbHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) as Neoadjuvant Treatment in HR +/HER2 + Breast Cancer

Sponsor

Shengjing Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05638594

Collaborator

(none)

236

Enrollment

Location

Arms

59.3

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an investigator-initiated randomized controlled, open-label, multicenter, prospective Phase 2 clinical study. Patients with stage II-III HR +/HER2 + breast cancer were randomly divided into two groups at a ratio of 1:1. The experimental group received pyrotinib combined with trastuzumab, dalpiciclib and letrozole; the control group received trastuzumab combined with pertuzumab, docetaxel and carboplatin. The main study objective was to evaluate the efficacy and safety of neoadjuvant therapy for HR +/HER2 + breast cancer in the two groups.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Pyrotinib Drug: Trastuzumab Drug: Dalpiciclib Drug: Letrozole Drug: Pertuzumab Drug: Docetaxel Drug: Carboplatin Drug: Gonadotropin-releasing hormone agonist	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

236 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Controlled, Open-label, Multicenter Clinical Study of Pyrotinib Maleate Combined With Trastuzumab,Dalpiciclib, and Letrozole Versus Trastuzumab Combined With Pertuzumab, Docetaxel, and Carboplatin as Neoadjuvant Therapy for Stage II-III HR +/HER2 + Breast Cancer

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Dec 10, 2025

Anticipated Study Completion Date :

Dec 10, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pyrotinib +trastuzumab+dalpiciclib+letrozole Every 4 weeks for 5 cycles. Cumulative 20 weeks of treatment. Premenopausal patients need to receive ovarian function suppression	Drug: Pyrotinib 320mg, qd Drug: Trastuzumab 8 mg/kg first dose, then 6 mg/kg，q3w Other Names: Herceptin Drug: Dalpiciclib 125mg , qd，d1-21, q4w Drug: Letrozole 2.5mg，qd Drug: Gonadotropin-releasing hormone agonist Every 4 weeks for 5 cycles, premenopausal patients only
Active Comparator: Trastuzumab + pertuzumab + docetaxel + carboplatin Every 3 weeks for 6 cycles. Cumulative 18 weeks of treatment	Drug: Trastuzumab 8 mg/kg first dose, then 6 mg/kg，q3w Other Names: Herceptin Drug: Pertuzumab 840 mg first dose, then 420 mg, q3w Other Names: Perjeta Drug: Docetaxel 75 mg/m2, q3w Drug: Carboplatin AUC 6, q3w

Arm

Intervention/Treatment

Experimental: Pyrotinib +trastuzumab+dalpiciclib+letrozole

Every 4 weeks for 5 cycles. Cumulative 20 weeks of treatment. Premenopausal patients need to receive ovarian function suppression

Drug: Pyrotinib

320mg, qd

Drug: Trastuzumab

8 mg/kg first dose, then 6 mg/kg，q3w

Other Names:

Herceptin

Drug: Dalpiciclib

125mg , qd，d1-21, q4w

Drug: Letrozole

2.5mg，qd

Drug: Gonadotropin-releasing hormone agonist

Every 4 weeks for 5 cycles, premenopausal patients only

Active Comparator: Trastuzumab + pertuzumab + docetaxel + carboplatin

Every 3 weeks for 6 cycles. Cumulative 18 weeks of treatment

Drug: Trastuzumab

8 mg/kg first dose, then 6 mg/kg，q3w

Other Names:

Herceptin

Drug: Pertuzumab

840 mg first dose, then 420 mg, q3w

Other Names:

Perjeta

Drug: Docetaxel

75 mg/m2, q3w

Drug: Carboplatin

AUC 6, q3w

Outcome Measures

Primary Outcome Measures

Pathologic Complete Response Rate (tpCR: ypT0-is/ypN0) [3 years]
Proportion of patients without any residual invasive cancer in pathological assessment of hematoxylin and eosin-stained resected breast cancer samples and all ipsilateral lymph node samples following completion of neoadjuvant therapy and surgery

Secondary Outcome Measures

Best overall response [3 years]
Proportion of patients with tumor response at any time during the study
Breast Pathologic Complete Response Rate (bpCR: ypT0-is) [3 years]
Proportion of patients without any residual invasive carcinoma in pathological assessment of hematoxylin and eosin stained resected breast cancer samples following completion of neoadjuvant therapy and surgery.
Residual cancer burden (RCB) [3 years]
RCB score is obtained according to pathological evaluation after completion of neoadjuvant treatment and surgery

Other Outcome Measures

Disease-free survival (DFS) [6 years]
It refers to the length of time from the start of medication after enrollment to the death of the patient because of the recurrence, distant metastasis of the disease, invasive contralateral breast cancer, or any other cause
Overall survival (OS) [10 years]
It refers to the length of time from the start of treatment to the death of the patient.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Female patients aged 18 -75 ;
Willing to receive LHRH agonist therapy (premenopausal patients only);
All patients were histopathologically confirmed to be estrogen receptor (ER) -positive and HER2-positive.
Treatment-naïve stage II-III patients with tumor stage meeting AJCC version 8 criteria;
ECOG score 0-1;
Organ function level must meet the following requirements:

(1) bone marrow function • ANC ≥ 1.5 x 109/L ; • PLT ≥ 100 × 109/L • Hb ≥ 90 g/L ; (2) hepatic and renal function • TBIL ≤ 1.5 × ULN; • AL and AST ≤ 3 × ULN (ALT and AST ≤ 5 × ULN in patients with liver metastases); • BUN and Cr ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min; (Cockcroft-Gault formula) (3) Echocardiography: LVEF ≥ 50%; (4) 12-lead ECG: QT interval ≤ 480 ms; 7. Able to undergo needle biopsy; 8. Voluntarily join this study to sign informed consent, have good compliance and willing to cooperate with follow-up.

Exclusion Criteria:

Received any form of anti-tumor therapy (chemotherapy, radiotherapy, molecular targeted therapy, endocrine therapy, etc.);
Received any other anti-tumor therapy at the same time;
Bilateral breast cancer, inflammatory breast cancer or occult breast cancer;
Stage IV breast cancer;
Breast cancer without histopathological diagnosis;
Other malignant tumors in the past 5 years, except cured cutaneous basal cell carcinoma and cervical carcinoma in situ;
Severe heart, liver and kidney and other vital organ dysfunction;
Inability to swallow, chronic diarrhea and intestinal obstruction, there are a variety of factors affecting drug administration and absorption;
Participated in other drug clinical trials within 4 weeks before enrollment;
Known history of hypersensitivity to the drug components of this protocol; history of immunodeficiency, including positive HIV test, HCV, active viral hepatitis B or other acquired, congenital immunodeficiency diseases, or history of organ transplantation;
Had any cardiac disease, including: (1) cardiac arrhythmia requiring medication or clinically significant; (2) myocardial infarction; (3) heart failure; (4) any other cardiac disease judged by the investigator to be inappropriate for participation in this trial;
Female patients who are pregnant or lactating, female patients of childbearing potential with a positive baseline pregnancy test, or female patients of childbearing age who are unwilling to take effective contraceptive measures throughout the trial;
According to the investigator 's judgment, there are concomitant diseases that seriously jeopardize the patient' s safety or affect the patient 's completion of the study (including but not limited to uncontrolled severe hypertension, severe diabetes, active infection, etc.);
Had a documented history of neurological or psychiatric disorders, including epilepsy or dementia.Any other condition that, in the opinion of the investigator, would make the patient inappropriate for participation in this study.