The Basket Study of Pyrotinib Maleate for HER2-Postive Solid Tumor

Study Overview
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Brief Summary
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This is an open-label, Phase 2 study exploring the efficacy and safety of 马来酸Pyrotinib Maleate Tablets in patients with solid tumors with activating（harmful） HER2 mutations or with HER2 gene amplification or immunohistochemical staining (IHC) assay showing HER2 is 3+ and / or fluorescence in situ hybridization (FISH) positive.

Official Title
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An Open-label, Phase 2 Study of Pyrotinib Maleate in Advanced Solid Tumors Patients With HER2( Erb-B2 Receptor Tyrosine Kinase 2)-Postive

Conditions
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Solid Tumor, HER2 Gene Mutation, HER-2 Gene Amplification, HER-2 Protein Overexpression

Intervention / Treatment
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* Drug: Pyrotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients between the ages of 18 and 75; ECOG physical status score 0-2 points; The estimated total survival period is not less than 12 weeks; Patients with HER2-positive solid tumors confirmed by pathology and identified as advanced tumors by clinicians or centers; HER2 positive: refers to standard immunohistochemical staining (IHC) assay showing HER2 is 3+ and / or fluorescence in situ hybridization (FISH) positive or after second generation sequencing shows HER2 amplification and copy number ≥ 3, or There is a HER2 activating mutation identified by the Molecular Oncology Committee (confirmed by the investigator at the test center) ; Imaging studies have at least one measurable lesion with a diameter ≥ 10 mm; Pilotinib has not been used for the past 3 months; The main organs function normally, they meet the following criteria: Blood routine examination criteria are to comply with: ①.Hb≥100 g/L; ②.ANC ≥ 1.5 × 109 / L; ③.PLT≥75×109 /L; Biochemical tests are subject to the following criteria ①.TBIL ≤ 1.5 × ULN (upper limit of normal value); ②.ALT and AST ≤ 2.5 × ULN; if there is liver metastasis, ALT and AST ≤ 5 × ULN; ③.Serum creatinine ≤ 1.5 × ULN, creatinine clearance ≥ 50ml / min (based on Cockroft and Gault formula); Heart color ultrasound: Left ventricular ejection fraction (LVEF) ≥ 50%; The patient or his legal guardian understands the test procedure and content and signs an informed consent form (ICF) to provide true and effective information in accordance with the research and follow-up procedures; Exclusion Criteria: There is a third interstitial fluid that cannot be controlled by drainage or other methods, such as pleural effusion and ascites; It has many factors affecting the oral and absorption of drugs (such as inability to swallow, postoperative gastrointestinal resection, chronic diarrhea and intestinal obstruction); Those who have been confirmed to be allergic to the drug components of this program; Patients who are known to be pregnant or planning to become pregnant, or gestational age patients who are unwilling to take effective contraceptive measures throughout the trial; Patients with severe concomitant diseases or those considered by the investigator to be unsuitable for inclusion. The investigator believes that the subject may not be able to complete the study or may not be able to comply with the requirements of the study (for administrative reasons or for other reasons).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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<br>This arm for HER2-postive solid tumor | Drug: Pyrotinib<br>* 400 mg administered orally, once daily, continuously in 21 day cycles<br>* Other names: SHR1258;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate defined as the patients confirmed complete response or partial response under RECIST 1.0 criteria. | at least 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Progression-free survival estimated using Kaplan-Meier methods is defined as the time from registration to the earlier of death or disease progression | up to 24 months | 
| Duration of Response | The first evaluation of treatment efficacy is the time fromcomplete response or partial response to the first assessment of disease progression or death from any cause. | up to 24 months | 
| Disease Control Rate | Objective response rate defined as the patients confirmed complete response or partial response or stable disease under RECIST 1.0 criteria. | up to 24 months | 
| Overall Survival | Overall survival estimated using Kaplan-Meier methods is defined as the time from treatment initiation to death by any cause | up to 36 months | 
| Safety (Adverse Events and Serious Adverse Events) | From consent through 28 days following treatment completion (estimated 6 months) | up to 36 months |