Efficacy and Safety of Pyrotinib in Patients With HER2 Mutation Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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Various driver gene mutations have been identified in lung cancer. Among them, human epidermal growth factor 2 (HER2) was identified in about approximately 2% of non-small cell lung cancers.Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This study is designed to evaluate the efficacy and safety of Pyrotinib in patients with HER2 positive advanced Non-small cell lung cancer.

Detailed Description
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This study is designed to evaluate the efficacy and safety of Pyrotinib in patients with HER2 positive advanced pre-treated Non-small cell lung cancer. To observe objective response rate (ORR) of pyrotinib in HER2 positive NSCLC. To observe Progression free survival （PFS）. To assess the overall survival (OS). To assess side effects. To evaluate quality of life. To explore the relationship between biomarkers and the toxicity/efficacy of Pyrotinib.

Official Title
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Single Arm Phase II Clinical Trial to Investigate the Efficacy and Safety of Pyrotinib as a Single Agent in HER2 Mutation Advanced Non-small Cell Lung Cancer Patients Who Failed to Previous at Least 2nd Line Treatments

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pyrotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 and ≤80 years. ECOG performance status of 0 to 1. Life expectancy of more than 12 weeks. At least one measurable lesion exists.(RECIST 1.1) Histologically or cytologic confirmed HER2 positive advanced Non-small cell lung cancer who failed prior therapies. Required laboratory values including following parameters: ANC: ≥ 1.5 x 10^9/L, Platelet count: ≥ 80 x 10^9/L, Hemoglobin: ≥ 90 g/L, Total bilirubin: ≤ 1.5 x upper limit of normal, ULN, ALT and AST: ≤ 1.5 x ULN, BUN and creatine clearance rate: ≥ 50 mL/min LVEF: ≥ 50% QTcF: < 470 ms Signed informed consent. Exclusion Criteria: Subjects with third space fluid that can not be controled by drainage or other methods. Subjects that are unable to swallow tablets, or dysfunction of gastrointestinal absorption. Less than 4 weeks from the last radiotherapy,chemotherapy,target therapy Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry. Subjects who can not interrupt the using of the drugs that may cause QT prolongation during study. Receiving any other antitumor therapy. Known history of hypersensitivity to pyrotinib or any of it components. Ongoing infection (determined by investigator). History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation. Subjects had any heart disease, including: (1) angina; (2) requiring medication or clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5) Any heart diseases judged by investigator as unsuitable to participate in the trial. Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test. Known history of neurological or psychiatric disease, including epilepsy or dementia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyrotinib treatment arm<br>pyrotinib treatment arm | Drug: Pyrotinib<br>* Drug: Pyrotinib pyrotinib, single agent, 400mg p.o once daily until disease progressed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | To evaluate objective response rate 6-8 weeks after the initiation of pyrotinib | tumor assessment every 6-8 weeks after the initiation of pyrotinib, up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | PFS is evaluated in 24 months since the treatment began | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pyrotinib, HER2, Non-small Cell Lung Cancer, Phase II