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

NCT06770296 | Recruiting Phase 1

• 1 other identifier: Photine-01
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

HER2 positive; Pyrotinib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Progression Free Survival

  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

  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

  From the first evaluation of CR, PR (whichever occurs first) to disease progression or death,whichever came first,assessed up to 100 months.

Study Arms (2)

Pyrotinib low dose group

EXPERIMENTAL

Pyrotinib: 320mg , peros(po) , once a day(qd) , every 3 weeks(q3w)

Drug: Pyrotinib low dose group

Pyrotinib normal dose group

ACTIVE COMPARATOR

Pyrotinib: 400mg , peros(po) , once a day(qd) , every 3 weeks(q3w)

Drug: Pyrotinib normal dose group

Interventions

Pyrotinib low dose group DRUG

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)

Pyrotinib low dose group

Pyrotinib normal dose group DRUG

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)

Pyrotinib normal dose group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: Patient is an adult female or male ≥ 18 years old and ≤ 75 years old at the time of informed consent.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• The First People's Hospital of Xuzhou: collaborator
• The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China: collaborator
• The Second People's Hospital of Changshu: collaborator
• Shuyang County Traditional Chinese Medicine Hospital: collaborator
• Affiliated Hospital of Nantong University: collaborator
• Affiliated Hospital of Jiangsu University: collaborator
• The Affiliated Hospital of Xuzhou Medical University: collaborator

Study Sites (1)

Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pyrotinib; Population Groups

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics

Study Officials

• Yongmei Yin, Ph.D

  The First Affiliated Hospital with Nanjing Medical University

  STUDY CHAIR

Central Study Contacts

Yongmei Yin, Ph.D

CONTACT

025-68307102; ymyin@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2024
• First Posted: January 13, 2025
• Study Start: November 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2028
• Last Updated: January 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)