Study of Apatinib Plus Etoposide Capsule as the Therapy of Advanced Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to confirm the safety and efficacy of Apatinib Plus Etoposide Capsule as the Therapy of Advanced Small Cell Lung Cancer.

Detailed Description
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Small cell lung cancer is a very aggressive cancer, often accompanied by distant metastases, with a poor prognosis. 5-year survival rate of less than 5%, untreated patients with an average survival of only 2-4 months. The investigators consider to add apatinib,a tyrosine kinase inhibitor of VEGF,to the therapy of these patients. The investigators designed the study to explore the possibility of apatinib Plus Etoposide Capsule as the Therapy of Advanced Small Cell Lung Cancer.

Official Title
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Single Arm, Exploratory and Open Phase II Clinical Trial of Apatinib Plus Etoposide Capsule as the Therapy of Advanced Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Apatinib and Etoposide Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological diagnosis of small cell lung cancer. ≥ 18 and ≤ 75 years of age. According to RESCIST1.1 standard, there are evaluable target lesions. Has received second-line standard treatment of recurrent or metastatic extensive stage small cell lung cancer. Life expectancy of more than 3 months. Eastern Cooperative Oncology Group(ECOG) performance status 0 or 2. Adequate hepatic, renal, heart, and hematologic functions: ANC ≥ 1.5×109/L, PLT ≥ 100×109/L, HB ≥ 90 g/L, TBIL ≤ 1.5×ULN, ALT or AST ≤ 2.5×ULN (or ≤ 5×ULN in patients with liver metastases), Serum Cr ≤ 1.25×ULN, Cr clearance ≥ 45 mL/min. Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 6 months after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 6 months after last dose of study drug. Signed the informed consent form prior to patient entry. Exclusion Criteria: Active brain metastases, meningococcal meningitis, patients with spinal cord compression, or imaging at CT or MRI examination revealed brain or pia mater disease（Patients who have completed treatment and whose symptoms are stable in the first 21 days of randomization may be enrolled in the study but may be diagnosed as having no intracerebral hemorrhage by MRI, CT or venography）； Imaging (CT or MRI) showed that the tumor lesions were ≤ 5 mm from the major vessels or there was a central tumor invading local macrovascular； Imaging (CT or MRI) showed significant cavitary or necrotic lung tumors, uncontrollable hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, despite optimal medical therapy), grade II The above myocardial ischemia or myocardial infarction, poor control of arrhythmia (including QTc interval male ≥ 450 ms, female ≥ 470 ms); NYHA standards, Ⅲ   Ⅳ grade cardiac insufficiency, or cardiac ultrasound examination prompted left ventricular ejection Score (LVEF) <50%； Coagulation dysfunction (INR> 1.5, PT> ULN +4s or APTT> 1.5 ULN), with bleeding tendency or ongoing thrombolysis or anti-blood coagulation treatment；Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or the like； Patients who had obvious hemoptysis within 2 months before screening, or experienced daily hemoptysis with a volume more than half a tea spoon (2.5ml) or above； Patients who experienced bleeding symptoms of clinical significance within 3 months before screening, or with confirmed bleeding tendency such as hemorrhage of digestive tract, hemorrhagic gastric ulcer, baseline occult blood in stool ++ and above, or vasculitis, etc. Patients who manifested arterial/venous thrombus events, e.g. cerebrovascular accident (Including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism, etc., within 12 months before screening（Such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism and so on）； Patients whose routine urine tests indicate that urine protein ≥ ++ or verifies that the 24-h urine protein quantitation ≥ 1.0 g； Previously used anti-angiogenic drugs.

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: Apatinib and Etoposide Capsule<br>Apatinib and Etoposide Capsule | Drug: Apatinib and Etoposide Capsule<br>* Apatinib 250mg/qd，po, A course of treatment need 28 days. Etoposide Capsule 25mg/d，po, from day 1-day 21.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | From date of randomization until the date of first documented progression or date of death from any cause | up to 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival(OS) | From date of randomization until the date of death from any cause | up to 2 year | 
| Objective Response Rate (ORR) | From date of randomization until the date of death from any cause | up to 1 year |