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

NCT ID: NCT05638594

Last Updated: 2023-03-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 236 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-20
• Study Completion Date: 2027-12-10

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pyrotinib +trastuzumab+dalpiciclib+letrozole

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

Group Type: EXPERIMENTAL

Pyrotinib

Intervention Type: DRUG

320mg, qd

Trastuzumab

Intervention Type: DRUG

8 mg/kg first dose, then 6 mg/kg，q3w

Dalpiciclib

Intervention Type: DRUG

125mg , qd，d1-21, q4w

Letrozole

Intervention Type: DRUG

2.5mg，qd

Gonadotropin-releasing hormone agonist

Intervention Type: DRUG

Every 4 weeks for 5 cycles, premenopausal patients only

Trastuzumab + pertuzumab + docetaxel + carboplatin

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

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: DRUG

8 mg/kg first dose, then 6 mg/kg，q3w

Pertuzumab

Intervention Type: DRUG

840 mg first dose, then 420 mg, q3w

Docetaxel

Intervention Type: DRUG

75 mg/m2, q3w

Carboplatin

Intervention Type: DRUG

AUC 6, q3w

Interventions

Pyrotinib

320mg, qd

Intervention Type: DRUG

Trastuzumab

8 mg/kg first dose, then 6 mg/kg，q3w

Intervention Type: DRUG

Dalpiciclib

125mg , qd，d1-21, q4w

Intervention Type: DRUG

Letrozole

2.5mg，qd

Intervention Type: DRUG

Pertuzumab

840 mg first dose, then 420 mg, q3w

Intervention Type: DRUG

Docetaxel

75 mg/m2, q3w

Intervention Type: DRUG

Carboplatin

AUC 6, q3w

Intervention Type: DRUG

Gonadotropin-releasing hormone agonist

Every 4 weeks for 5 cycles, premenopausal patients only

Intervention Type: DRUG

Other Intervention Names

Herceptin; Perjeta

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Shengjing Hospital

OTHER

Sponsor Role: lead

Responsible Party

Caigang Liu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shengjing Hospital of China Medical University

Shenyang, Liaoning, China

Site Status: RECRUITING

Countries

China

Central Contacts

Nan Niu

Role: CONTACT

niunannancy@163.com

+8618940256668

Facility Contacts

Cai-Gang Liu, PHD

Role: primary

liucg@sj-hospital.org

+86 18940254967

References

Huo S, Xue J, Wang S, Shan H, Chen G, Niu N, Wang Y, Qiu F, Zhao Y, Xing F, Zheng X, Tu W, Li K, Zhao H, Tang M, Xu Q, Liu C, Zhao Y, Jiang X, Pang Z, Zhang K, Zhang D, Chen ZS, Liu C. A pilot trial of neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer. MedComm (2020). 2024 Mar 10;5(3):e505. doi: 10.1002/mco2.505. eCollection 2024 Mar.

Reference Type: DERIVED

PMID: 38469548 (View on PubMed)

Other Identifiers

MUKDEN-09

Identifier Type: -

Identifier Source: org_study_id