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

Phase 2

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Pyrotinib; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Dalpiciclib; Drug: Docetaxel; Drug: Carboplatin; Drug: Letrozole; Drug: Gonadotropin-releasing hormone agonist

• Registration Number: NCT05638594
• Lead Sponsor: Shengjing Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-24
• Study First Submitted QC: 2022-12-02
• Study First Posted: 2022-12-06
• Study Start: 2022-12-20
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-16
• Last Update Posted: 2023-03-20
• Primary Completion: 2025-12-10
• Study Completion: 2027-12-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 236

Inclusion Criteria

1. Female patients aged 18 -75 ;
2. Willing to receive LHRH agonist therapy (premenopausal patients only);
3. All patients were histopathologically confirmed to be estrogen receptor (ER) -positive and HER2-positive.
4. Treatment-naïve stage II-III patients with tumor stage meeting AJCC version 8 criteria;
5. ECOG score 0-1;
6. 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

1. Received any form of anti-tumor therapy (chemotherapy, radiotherapy, molecular targeted therapy, endocrine therapy, etc.);
2. Received any other anti-tumor therapy at the same time;
3. Bilateral breast cancer, inflammatory breast cancer or occult breast cancer;
4. Stage IV breast cancer;
5. Breast cancer without histopathological diagnosis;
6. Other malignant tumors in the past 5 years, except cured cutaneous basal cell carcinoma and cervical carcinoma in situ;
7. Severe heart, liver and kidney and other vital organ dysfunction;
8. Inability to swallow, chronic diarrhea and intestinal obstruction, there are a variety of factors affecting drug administration and absorption;
9. Participated in other drug clinical trials within 4 weeks before enrollment;
10. 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;
11. 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;
12. 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;
13. 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.);
14. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Trastuzumab + pertuzumab + docetaxel + carboplatin	Carboplatin	Every 3 weeks for 6 cycles. Cumulative 18 weeks of treatment
Pyrotinib +trastuzumab+dalpiciclib+letrozole	Gonadotropin-releasing hormone agonist	Every 4 weeks for 5 cycles. Cumulative 20 weeks of treatment. Premenopausal patients need to receive ovarian function suppression
Pyrotinib +trastuzumab+dalpiciclib+letrozole	Trastuzumab	Every 4 weeks for 5 cycles. Cumulative 20 weeks of treatment. Premenopausal patients need to receive ovarian function suppression
Trastuzumab + pertuzumab + docetaxel + carboplatin	Pertuzumab	Every 3 weeks for 6 cycles. Cumulative 18 weeks of treatment
Pyrotinib +trastuzumab+dalpiciclib+letrozole	Pyrotinib	Every 4 weeks for 5 cycles. Cumulative 20 weeks of treatment. Premenopausal patients need to receive ovarian function suppression
Pyrotinib +trastuzumab+dalpiciclib+letrozole	Dalpiciclib	Every 4 weeks for 5 cycles. Cumulative 20 weeks of treatment. Premenopausal patients need to receive ovarian function suppression
Pyrotinib +trastuzumab+dalpiciclib+letrozole	Letrozole	Every 4 weeks for 5 cycles. Cumulative 20 weeks of treatment. Premenopausal patients need to receive ovarian function suppression
Trastuzumab + pertuzumab + docetaxel + carboplatin	Trastuzumab	Every 3 weeks for 6 cycles. Cumulative 18 weeks of treatment
Trastuzumab + pertuzumab + docetaxel + carboplatin	Docetaxel	Every 3 weeks for 6 cycles. Cumulative 18 weeks of treatment

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Best overall response	3 years	Proportion of patients with tumor response at any time during the study
Residual cancer burden (RCB)	3 years	RCB score is obtained according to pathological evaluation after completion of neoadjuvant treatment and surgery
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.

Trial Locations

Locations (1)

Shengjing Hospital of China Medical University; 🇨🇳 Shenyang, Liaoning, China