The Dosing Regimen of Pyrotinib in HER2-positive Advanced First-line Breast Cancer: a Phase I Clinical Study

Phase 1

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Pyrotinib low dose group; Drug: Pyrotinib normal dose group

• Registration Number: NCT06770296
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

Brief Summary

Evaluate the safety and efficacy of Pyrotinib at different doses in combination with trastuzumab and paclitaxel chemotherapy for first-line treatment of HER2-positive advanced breast cancer.

Detailed Description

This study is planned to include 200 patients with HER2-positive advanced breast cancer meeting the admission criteria between 2024-11-01 and 2026-11-01. Statistical software will be used by the randomization officers for 1:1 allocation to pyrotinib 320mg in combination with trastuzumab and paclitaxel chemotherapy group and pyrotinib 400mg in combination with trastuzumab and paclitaxel chemotherapy group.

Study Timeline

• Study Start: 2024-11-01
• Study First Submitted: 2024-12-19
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-07
• Last Update Submitted: 2025-01-07
• Study First Posted: 2025-01-13
• Last Update Posted: 2025-01-13
• Primary Completion: 2026-11-01
• Study Completion: 2028-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• The subjects voluntarily joins the study and signs the informed consent;
• Subject is an adult female or male ≥ 18 years old and ≤ 75 years old at the time of informed consent;
• HER2-positive advanced breast cancer confirmed by pathology:HER2-positive was defined as >10% of immunoreactive cells with an immunohistochemical (IHC) score of 3+ or HER2 gene amplification as a result of in situ hybridization (ISH). HER2 positivity should be verified by the pathology department of the research center;
• Recurrent or metastatic breast cancer; Patients with local recurrence had to be confirmed by the investigator as not amenable to curative resection;
• At least one measurable lesion or only bone metastases according to RECIST v1.1 criteria (including osteolytic lesions or mixed osteolytic/osteoblastic lesions);
• When randomized, Eastern Cooperative Oncology Group(ECGO) physical fitness status is 0 or 1 point;
• Vital organ function meets the following requirements (excluding the use of any blood components and cell growth factors during screening) : Absolute neutrophil (ANC) count ≥1.5×109/L; Platelet (PLT) ≥100×109/L; Hemoglobin (HB) ≥9g/dL; Total Bilirubin(TBIL) ≤ULN((Known patients with Gilbert's syndrome:Total Bilirubin(TBIL) ≤2×ULN);Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5×ULN(Patients with liver metastasis:ALT and AST≤5×ULN); Alkaline phosphatase (AKP) ≤ 2.5 times ULN; Blood Urea Nitrogen and Serum creatinine (Cr) ≤1.5×ULN;Left Ventricular Ejection Fractions(LVEF)≥50%;Corrected QT Interval(QTcF)<470msec.

Exclusion Criteria

• The patient has received any systemic antitumor therapy at the stage of recurrence/metastasis, including any agents targeting EGFR or HER2, systemic chemotherapy, immunotherapy, and more than first-line endocrine therapy, as well as other antitumor therapies deemed by the investigators to be excluded;
• Tyrosine kinase inhibitor (TKI) preparations or macromolecular antibodies against HER have been used at any stage of breast cancer, except for trastuzumab in the (new) adjuvant stage;
• In the stage of breast cancer (new) adjuvant therapy, the time interval from the end of systemic therapy (except endocrine therapy) to the discovery of recurrence/metastasis is <12 months;
• Patients with active brain metastases with pial metastases confirmed by MRI or lumbar puncture (brain metastases requiring mannitol treatment or with symptoms);
• Grade≥ 3 peripheral neuropathy according to CTCAE4.0.3 criteria;
• Patients judged by the investigators to be unsuitable for systematic chemotherapy;
• Use of endocrine therapy drugs within 7 days prior to randomization;
• Patients with other malignancies within the previous 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma, or squamous cell carcinoma (patients with other malignancies occurring more than 5 years after randomization, such as those cured only by surgery, are allowed to be included);
• Had a major surgical procedure or significant trauma within 4 weeks prior to randomization, or was expected to undergo major surgery;
• Serious heart disease or discomfort, including but not limited to the following:

Previous history of heart failure or systolic dysfunction (LVEF<50%) High-risk or treatment-requiring angina pectoris or arrhythmias (e.g., second-degree type 2 atrioventricular block or third-degree atrioventricular block, ventricular tachycardia) Clinically significant valvular heart disease ECG showed transmural myocardial infarction Poor hypertension control (systolic blood pressure >150mmHg and/or diastolic blood pressure >100mmHg);

• Inability to swallow, chronic diarrhea, intestinal obstruction, or other factors affecting the administration and absorption of medications;
• Known allergic history of the drug components of this protocol;
• A history of immunodeficiency, including HIV infection, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation;
• Presence of third-space fluid accumulation that cannot be controlled by drainage or other methods (e.g., pleural fluid and ascites);
• Pregnant and lactating female subjects, or fertile subjects who were unwilling to use effective contraception throughout the trial period and within 3 months after the last study dose;
• Have a serious concomitant disease or other co-medical condition that interferes with planned treatment or any other condition that is not suitable for participation in this study, such as active hepatitis B, a lung infection requiring treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Pyrotinib low dose group	Pyrotinib low dose group	Pyrotinib: 320mg , peros(po) , once a day(qd) , every 3 weeks(q3w)
Pyrotinib normal dose group	Pyrotinib normal dose group	Pyrotinib: 400mg , peros(po) , once a day(qd) , every 3 weeks(q3w)

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	From the time of initiation of treatment in this study to the time of disease progression in the subjects,assessed up to 100 months.	Objective Response Rate refers to the percentage of the total number of subjects in the analyzed data set who achieved the best response of CR or PR from the beginning of the study treatment to the time of the subject's disease progression group. Response Evaluation criteria in Solid Tumors (RECIST 1.1) was recommended to assess objective tumor response. Participants had to have measurable tumor lesions at baseline, and the response evaluation criteria were recommended as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST 1.1 criteria.

Trial Locations

Locations (1)

Jiangsu Provincial People's Hospital; 🇨🇳 Nanjing, Jiangsu, China