Efficacy and Safety of Pyrotinib in HER2 Positive Gastrointestinal Tumors

Study Overview
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Brief Summary
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Targeting human epidermal factor receptor 2 (HER2) therapy have shown the anti-tumor efficacy in patients with HER2-positive gastrointestinal tumors. Pyrotinib is an irreversible small-molecule receptor tyrosine kinase inhibitor targeting both epidermal growth factor receptor (EGFR) and HER2. This study is designed to evaluate the efficacy and safety of Pyrotinib in patients with HER2 positive gastrointestinal tumors.

Detailed Description
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This study is designed to evaluate the efficacy and safety of Pyrotinib in patients with HER2 positive gastrointestinal tumors. Three cohorts were designed for this trial. Cohort 1: patients with gastric cancer or esophageal adenocarcinoma receiving paclitaxel combined with pyrotinib for second-line therapy; Cohort 2: patients with gastric cancer or esophageal adenocarcinoma receiving pyrotinib monotherapy for third-line or posterior line therapy; Cohort 3: patients with colorectal cancer receiving pyrotinib combined with/without trastuzumab for third-line or posterior line therapy.

Official Title
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Efficacy and Safety of Pyrotinib in Patients With HER2 Positive Refractory or Metastatic Gastrointestinal Tumors

Conditions
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Gastrointestinal Tumor, Effect of Drug

Intervention / Treatment
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* Drug: Pyrotinib with or without trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 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 gastrointestinal tumors 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

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<br>Pyrotinib with or without paclitaxel/trastuzumab treatment | Drug: Pyrotinib with or without trastuzumab<br>* After enrollment, patients of all the three cohorts were given 400 mg/d oral pyrotinib continuously, every 21 days as a cycle; Cohort 1 and 2 : Patients with gastric cancer or esophageal adenocarcinoma were combined with paclitaxel 80 mg/m2, intravenously, once on the first and eighth day. Cohort 3: Patients with colorectal cancer were given trastuzumab at an initial load dose of 8 mg/kg followed by 6 mg/kg every 3 weeks.<br>* Other names: pyrotinib with other drugs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | evaluated in the 24th month since the treatment began | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | evaluated in the 24th month 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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pyrotnib, HER2, Gastrointestinal Tumor, Phase II