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

Safety and Efficacy of Pyrotinib in Transition From a Low-dose to Normal-dose Regimen in HER2-positive Advanced First-line Breast Cancer: a Multicenter, Open Phase II Clinical Study

Evaluate the safety and efficacy of Pyrotinib in the transition from low-dose to normal-dose regimen for HER2-positive advanced first-line breast cancer

Study Overview

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

Detailed Description

This study is planned to include 102 patients with HER2-positive advanced breast cancer meeting the admission criteria between 2023-12-01 and 2024-11-01. Statistical software will be used by the randomization officers for 1:1 allocation to pyrotinib dose increasing trial group and normal pyrotinib dose control group .

The primary endpoint of this study was grade ≥3 treatment-emergent diarrhea incidence during the first 2 cycles according to Common Terminology Criteria for Adverse Events, version 5.0, and secondary endpoints were adverse effects of pyrotinib during the study, efficacy (progression-free survival and overall survival), and patient-reported outcome.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 2

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The subjects voluntarily joins the study and signs the informed consent;
2. Subject is an adult female ≥ 18 years old and ≤ 70 years old at the time of informed consent.
3. HER2-positive advanced breast cancer confirmed by pathology (HER2-positive expression refers to those with at least one tumor cell immunohistochemical staining intensity of 3+ or 2+ positive by fluorescence in situ hybridization [FISH] in the pathological examination/review of the primary or metastatic lesion conducted by the pathology department of the Central Hospital)
4. Stage IV breast cancer according to American Joint Committee on Cancer(AJCC) staging system version 8.
5. Subjects did not receive systemic antitumor therapy at the stage of recurrence/metastasis;
6. At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors version 1.1 criteria
7. When randomized, Eastern Cooperative Oncology Group(ECGO) physical fitness status is 0 or 1 point.
8. 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; Serum albumin ≥3g/dL; Thyroid stimulating hormone (TSH) ≤ULN (if abnormal, T3 and T4 levels should be investigated at the same time, if T3 and T4 levels are normal, they can be included in the group); Bilirubin ≤1.5 ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times ULN; Alkaline phosphatase (AKP) ≤ 2.5 times ULN; Serum creatinine (Cr) ≤1.5 times ULN or creatinine clearance ≥60mL/min.

Exclusion Criteria:

1. Any previous tyrosine kinase inhibitor therapy against HER2 target;
2. Patients with known active central nervous system metastases without surgery or radiation therapy, except those who have been stable for at least 1 month after treatment and have been off corticosteroids for >2 weeks;
3. Pial metastasis confirmed by MRI or lumbar puncture;
4. Inflammatory breast cancer or other malignancies within the previous 5 years, excluding cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;
5. Any antitumor therapy within 4 weeks prior to enrollment;
6. Pregnant or breastfeeding women (women of childbearing age must have a negative pregnancy test within 14 days prior to the first dose, if positive, the pregnancy must be ruled out by ultrasound);
7. Patients with gastrointestinal insufficiency or gastrointestinal disease significantly affecting the absorption of the investigational drug (e.g., uncontrolled ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or resection of the small intestine);
8. Patients with ascites, pleural effusion and pericardial effusion accompanied by clinical symptoms requiring drainage at baseline, or patients with serosal effusion drainage within 4 weeks before the first medication;
9. Patients with a history of immunodeficiency, including HIV testing positive, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
10. Patients with a major surgical procedure or significant trauma within 4 weeks before starting treatment, or expected to undergo major surgery;
11. Concomitant medical conditions (e.g., severe hypertension, diabetes, thyroid disease, co-active hepatitis B/C, and other active infections, etc.) that are deemed by the investigator to seriously endanger the patient's safety or to interfere with the patient's completion of the study;
12. Inability to understand or follow research instructions and requirements;
13. The investigator considers the patient unsuitable for entry into this study.

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 dose escalation group; Pyrotinib: 240mg in the first week, 320mg in the second week, and 400mg in the third week and thereafter, by mouth(po),once a day(qd)	Drug: Pyrotinib dose escalation; Pyrotinib: 240mg in the first week, 320mg in the second week, and 400mg in the third week and thereafter, by mouth(po),once a day(qd) 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); Other Names: Trastuzumab; Docetaxel
Active Comparator: Pyrotinib dose normal group; Pyrotinib: 400mg per week, by mouth(po),once a day(qd)	Drug: Pyrotinib dose normal; Pyrotinib: 400mg per week, by mouth(po),once a day(qd) 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); Other Names: Trastuzumab; Docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of 2 cycles ≥ grade 3 diarrhea	Grade ≥3 treatment-emergent diarrhea incidence at the end of the first 2 cycles（each cycle is 28 days） according to Common Terminology Criteria for Adverse Events(CTCAE) v5.0.	From the date of enrollment to 2 cycles（each cycle is 28 days） of the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Adverse events include abnormal liver function, myelosuppression and so on.	through study completion, an average of 1 year(From the date of enrollment to 30 days after the last dose)
Progression Free Survival	Progression-free survival is defined as the time from the date of randomization to the date of the first documented progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death due to any cause.	From date of randomization until the date of first documented progression 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 due to any cause.	From date of randomization until the date of death from any cause, 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)

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: Anhui Provincial Cancer Hospital; Affiliated Hospital of Jiangnan University; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; Zhongda Hospital; Affiliated Hospital of Jiangsu University; The Affiliated Hospital of Xuzhou Medical University; Suzhou Municipal Hospital; Affiliated Hospital of Nantong University; Huai'an First People's Hospital; Jingjiang People's Hospital; Yancheng First People's Hospital
• Investigators: Study Chair: Yongmei Yin, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: January 28, 2024
• First Submitted That Met QC Criteria: February 4, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: HER2 positive; Pyrotinib
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Trastuzumab
• Other Study ID Numbers: Photine

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