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

Pyrotinib at Different Doses in Combination With Trastuzumab and Paclitaxel Chemotherapy for First-Line Treatment of HER2-Positive Advanced Breast Cancer: A Multicenter, Randomized, Double-Cohort Study

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib low dose group; Drug: Pyrotinib normal dose group

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 Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yongmei Yin, Ph.D; Phone Number: 025-68307102; Email: ymyin@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Jiangsu Provincial People's Hospital
      • Contact: Yongmei Yin, Ph.D; Phone Number: 025-68307102; Email: ymyin@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pyrotinib low dose group; Pyrotinib: 320mg , peros(po) , once a day(qd) , every 3 weeks(q3w)	Drug: Pyrotinib low dose group; Pyrotinib: 320mg, peros(po),once a day(qd) ,every 3 weeks(q3w) Trastuzumab: 8mg/Kg in the first cycle, 6mg/Kg in the subsequent cycle, intravenous(iv), every 3 weeks(q3w) Docetaxel: 75mg/m2，intravenous(iv), every 3 weeks(q3w)
Active Comparator: Pyrotinib normal dose group; Pyrotinib: 400mg , peros(po) , once a day(qd) , every 3 weeks(q3w)	Drug: Pyrotinib normal dose group; Pyrotinib: 400mg, peros(po),once a day(qd) ,every 3 weeks(q3w) Trastuzumab: 8mg/Kg in the first cycle, 6mg/Kg in the subsequent cycle, intravenous(iv), every 3 weeks(q3w) Docetaxel: 75mg/m2，intravenous(iv), every 3 weeks(q3w)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	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.	From the time of initiation of treatment in this study to the time of disease progression in the subjects,assessed up to 100 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression Free Survival refers to the time from the day of randomization until the first imaging assessment of disease progression (PD) or death from any cause. If subjects do not develop PD or die by the study deadline, or have received other antitumor therapy, the cut-off time will be based on the results of the last efficacy assessment before the deadline date or the start date of other antitumor therapy, whichever comes first.	From date of randomization until the date of first documented progression or death from any cause, whichever came first,assessed up to 100 months.
Overall survival	Overall survival is defined as the time from the date of randomization to the date of death from any cause. For subjects who were still alive at the last follow-up, the OS was deleted based on the last follow-up time. For subjects who were lost to follow-up, the OS was calculated as the last confirmed survival time before the lost follow-up.	From date of randomization until the date of first documented progression or death from any cause, whichever came first,assessed up to 100 months.
Duration of Response	Duration of Response refers to the time period from the first evaluation of CR, PR (whichever occurs first) to disease progression or death. RECIST 1.1 standard was used for evaluation.	From the first evaluation of CR, PR (whichever occurs first) to disease progression or death,whichever came first,assessed up to 100 months.
Patient report outcome	The rating is evaluated by Functional Assessment of Cancer Therapy-Breast scale. It contains questions in five dimensions, with scores ranging from 0 to 4 for each question, with higher scores generally indicating a better quality of life	Through study completion, an average of 1 year(From the date of enrollment to the clinical outcome from patients' report)
Incidence of Treatment-Emergent Adverse Events	Adverse events include abnormal liver function, myelosuppression and so on.	From the beginning of the patient's use of pyrrotinib until the end of the safety follow-up period (28 days after the last dose).

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: Affiliated Hospital of Jiangsu University; The Affiliated Hospital of Xuzhou Medical University; The First People's Hospital of Xuzhou; Affiliated Hospital of Nantong University; The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China; The Second People's Hospital of Changshu; Shuyang County Traditional Chinese Medicine Hospital
• Investigators: Study Chair: Yongmei Yin, Ph.D, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: December 19, 2024
• First Submitted That Met QC Criteria: January 7, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 7, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: HER2 positive; Pyrotinib
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: Photine-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No