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

NCT06254690 | Recruiting Phase 2

• 1 other identifier: Photine
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Breast Cancer

Keywords

HER2 positive; Pyrotinib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Incidence of Treatment-Emergent Adverse Events

  through study completion, an average of 1 year(From the date of enrollment to 30 days after the last dose)

• Progression Free Survival

  From date of randomization until the date of first documented progression from any cause, whichever came first, assessed up to 100 months

• Overall survival

  From date of randomization until the date of death from any cause, assessed up to 100 months

• Patient report outcome

  through study completion, an average of 1 year(From the date of enrollment to the clinical outcome from patients' report)

Study Arms (2)

Pyrotinib dose escalation group

EXPERIMENTAL

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 dose normal group

ACTIVE COMPARATOR

Pyrotinib: 400mg per week, by mouth(po),once a day(qd)

Drug: Pyrotinib dose normal

Interventions

Pyrotinib dose escalation DRUG

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)

Also known as: Trastuzumab, Docetaxel

Pyrotinib dose escalation group

Pyrotinib dose normal DRUG

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)

Also known as: Trastuzumab, Docetaxel

Pyrotinib dose normal group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Patient is an adult female ≥ 18 years old and ≤ 70 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 ≥ 18 years old and ≤ 70 years old at the time of informed consent.
• 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)
• Stage IV breast cancer according to American Joint Committee on Cancer(AJCC) staging system version 8.
• Subjects did not receive systemic antitumor therapy at the stage of recurrence/metastasis;
• At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors version 1.1 criteria
• 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; 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.

You may not qualify if:

• Any previous tyrosine kinase inhibitor therapy against HER2 target;
• 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;
• Pial metastasis confirmed by MRI or lumbar puncture;
• 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;
• Any antitumor therapy within 4 weeks prior to enrollment;
• 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);
• 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);
• 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;
• Patients with a history of immunodeficiency, including HIV testing positive, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
• Patients with a major surgical procedure or significant trauma within 4 weeks before starting treatment, or expected to undergo major surgery;
• 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;
• Inability to understand or follow research instructions and requirements;
• The investigator considers the patient unsuitable for entry into this study.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• Zhongda Hospital: collaborator
• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: collaborator
• Jingjiang People's Hospital: collaborator
• Yancheng First People's Hospital: collaborator
• Affiliated Hospital of Jiangnan University: collaborator
• Affiliated Hospital of Nantong University: collaborator
• Anhui Provincial Cancer Hospital: collaborator
• Huai'an First People's Hospital: collaborator
• The Affiliated Hospital of Xuzhou Medical University: collaborator
• Suzhou Municipal Hospital: collaborator
• Affiliated Hospital of Jiangsu University: collaborator

Study Sites (1)

Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Docetaxel

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; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Yongmei Yin

  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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2024
• First Posted: February 12, 2024
• Study Start: January 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 12, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)