Stereotactic Radiosurgery Combination With Anlotinib for Limited Brain Metastases With Perilesional Edema in NSCLC

Study Overview
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Brief Summary
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The purpose of this study is to determine whether stereotactic radiosurgery combination with Anlotinib is safe, effective in the treatment of limited brain metastases with Perilesional edema in non-small cell lung cancer.

Detailed Description
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The purpose of this study is to determine whether stereotactic radiosurgery combination with Anlotinib is safe, effective in the treatment of limited brain metastases with perilesional edema in non-small cell lung cancer. The sample size is 50. Patients start to take Anlotinib 1 week before the MRI-based simulation，12mg/d QD，day1 14, day22 36.Edema index will be used to evaluate the effectiveness of Anlotinib. The Edema index (EI) is calculated per the equation of edema index= (peri-tumoral edema volume+ tumor volume)/tumor volume.

Official Title
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Stereotactic Radiosurgery Combination With Anlotinib for Limited Brain Metastases With Perilesional Edema in Non-small Cell Lung Cancer：An Exploratory Single-Arm Phase II Clinical Trail

Conditions
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Stereotactic Body Radiation Therapy

Intervention / Treatment
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* Drug: Anlotinib
* Radiation: Stereotactic Radiosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients voluntarily participate in this study, signed informed consent. Patients pathologically diagnosed as non-small cell lung cancer, with brain metastases and measurable lesions; Patients aged between 18 -80 years; with expected survival time>3 months. Patients with no more than 5 brain metastases Patients with normal organ function within 7 days prior to treatment, the following criteria are met: a) blood routine examination criteria : i) hemoglobin (HB) ≥90g/L; ii) absolute neutrophil count (ANC) ≥1.5×10e9/L; iii) platelet (PLT) ≥80×10e9/L; b) biochemical tests meet the following criteria: i) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); ii) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 ULN, if liver metastasis occurred, ALT and AST ≤5 ULN; iii) serum creatinine (Cr) ≤1.5 ULN or creatinine clearance (CCr) ≥60mL/min; Female patients should agree to use contraceptives during and within 6 months after the study. Exclusion Criteria: Patients who had previously used antiangiogenic agents within 1 month; Patients with small cell lung cancer (including small cell carcinoma and non-small cell carcinoma mixed lung cancer); Patient with lung squamous cell carcinoma that involved pulmonary hilar, or non-small cell lung cancer with hemoptysis; Patients with cerebral infarction and cerebral hemorrhage; Patients without perilesional edema； Patients with more than grade 2 (NCI-CTCAE v4.0) acute toxicity reaction due to any previous treatment. Patients with factors that affect oral medication (such as cannot swallow, chronic diarrhea and intestinal obstruction, etc.); Patients with visceral dissemination or severe symptoms, which could cause death in short term; Patients with any other severe and/or uncontrolled disease; Patients who received a surgery, a biopsy or a significant traumatic injury within 1 month; Patients with any signs or medical history of bleeding, unhealed wounds, ulcers or fractures, regardless of the severity; Patients underwent artery or venous thrombotic events within 2 months, such as deep vein thrombosis and pulmonary embolism; Patients with a history of psychotropic medicine abuse and cannot quit or have mental disorders; Patients with disease which will severely endanger their security and could not complete this study, according to the judgement of researchers； Patients who still can't tolerate SRS after anlotinib treatment, even after adding mannitol, and have to receive steroid treatment.

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: SRS Combination With Anlotinib<br>Stereotactic Radiosurgery Combination With Anlotinib | Drug: Anlotinib<br>* Anlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD α/β, c-Kit and Ret.<br>* Other names: Antiangiogenic agents;Radiation: Stereotactic Radiosurgery<br>* Stereotactic Radiosurgery as the initial treatment of non small cell lung cancer patients with limited brain metastases<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EI | Edema Index. The Edema index (EI) is calculated per the equation of edema index= (peri-tumoral edema volume+ tumor volume)/tumor volume. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free Survival | 1 year | 
| OS | Overall Survival | 1 year | 
| ORR | Objective Response Rate | 3 months | 
| DCR | Disease Control Rate | 3 months | 
| iORR | intracranial objective response rate | 3 months | 
| iPFS | intracranial progression-free survival | 3 months | 
| SRS rate | the rate of SRS after anlotinib treatment | 1 month |