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

NCT05638594 | Recruiting Phase 2

• 1 other identifier: MUKDEN-09
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response Rate (tpCR: ypT0-is/ypN0)

  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

  3 years

Secondary Outcomes (3)

• Best overall response

  3 years

• Breast Pathologic Complete Response Rate (bpCR: ypT0-is)

  3 years

• Residual cancer burden (RCB)

  3 years

Other Outcomes (2)

• Disease-free survival (DFS)

  6 years

• Overall survival (OS)

  10 years

Study Arms (2)

Pyrotinib +trastuzumab+dalpiciclib+letrozole

EXPERIMENTAL

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

Drug: Pyrotinib; Drug: Trastuzumab; Drug: Dalpiciclib; Drug: Letrozole; Drug: Gonadotropin-releasing hormone agonist

Trastuzumab + pertuzumab + docetaxel + carboplatin

ACTIVE COMPARATOR

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

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Docetaxel; Drug: Carboplatin

Interventions

Pyrotinib DRUG

320mg, qd

Pyrotinib +trastuzumab+dalpiciclib+letrozole

Trastuzumab DRUG

8 mg/kg first dose, then 6 mg/kg，q3w

Also known as: Herceptin

Pyrotinib +trastuzumab+dalpiciclib+letrozole; Trastuzumab + pertuzumab + docetaxel + carboplatin

Dalpiciclib DRUG

125mg , qd，d1-21, q4w

Pyrotinib +trastuzumab+dalpiciclib+letrozole

Letrozole DRUG

2.5mg，qd

Pyrotinib +trastuzumab+dalpiciclib+letrozole

Pertuzumab DRUG

840 mg first dose, then 420 mg, q3w

Also known as: Perjeta

Trastuzumab + pertuzumab + docetaxel + carboplatin

Docetaxel DRUG

75 mg/m2, q3w

Trastuzumab + pertuzumab + docetaxel + carboplatin

Carboplatin DRUG

AUC 6, q3w

Trastuzumab + pertuzumab + docetaxel + carboplatin

Gonadotropin-releasing hormone agonist DRUG

Every 4 weeks for 5 cycles, premenopausal patients only

Pyrotinib +trastuzumab+dalpiciclib+letrozole

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shengjing Hospital: lead

Study Sites (1)

Shengjing Hospital of China Medical University

Shenyang, Liaoning, 110004, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 38469548 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pyrotinib; Trastuzumab; dalpiciclib; Letrozole; pertuzumab; Docetaxel; Carboplatin; Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Coordination Complexes; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Oligopeptides; Nerve Tissue Proteins

Central Study Contacts

Nan Niu

CONTACT

+8618940256668; niunannancy@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 24, 2022
• First Posted: December 6, 2022
• Study Start: December 20, 2022
• Primary Completion: December 10, 2025
• Study Completion (Estimated): December 10, 2027
• Last Updated: March 20, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)