Anlotinib Plus Etoposide and Carboplatin as First-line Treatment for Extensive-stage Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
This is a phase II, open-label, single center study, aiming to investigate safety and efficacy of etoposide and carboplatin (administered intravenously) in combination with anlotinib (administered orally) in treatment-naive advanced NSCLC.

Detailed Description
-----------------
Lung cancer can be divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), of which SCLC accounts for about 15%-20%.Because of the high degree of malignancy of SCLC, patients often lose the opportunity of surgical treatment due to metastasis at the time of admission. Traditional cytotoxic drugs can improve the prognosis of patients and life treatment, but the survival benefit is very limited. Vascular targeted therapy is an important treatment strategy for metastatic lung cancer.Anlotinib hydrochloride is a multi-target receptor tyrosine kinase inhibitor that has significant inhibitory activity against angiogenesis related kinases such as VEGFR1/2/3, FGFR1/2/3, and other tumor related kinases such as PDGFR /, C-Kit, Ret, etc. (e.g., Met, FGFR1/2/3). An exploratory phase II study explored the efficacy of third-line single-drug therapy for ED-SCLC and found significant improvement in prognosis. Based on the above status and research results, the purpose of this study was to explore the efficacy and safety of anlotinib hydrochloride combined with etoposide/carboplatin in first-line treatment of extensive small-cell lung cancer.

Official Title
-----------------
Anlotinib Plus Etoposide and Carboplatin as First-line Treatment for Extensive-stage Small Cell Lung Cancer: A Single Arm Phase II Trial

Conditions
-----------------
SCLC, Anlotinib

Intervention / Treatment
-----------------
* Drug: Anlotinib hydrochloride
* Drug: Etoposide
* Drug: Carboplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with extensive stage SCLC confirmed by histology or cytology and are confirmed to have at least one measurable lesion according to RECIST 1.1. Without active brain metastasis Previously treated with ICIs with progressive disease. Age ≥18 years and ≤75 years; ECOG PS score: 0 to 1 The main organs function is normal, that is, the following criteria met: good hematopoietic function, defined as absolute neutrophil count ≥1.5×109 /L, platelet count≥100 ×109 /L, hemoglobin ≥90g/L [no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment]; biochemical test results should meet the following criteria: BIL < 1.25 times the upper limit of normal value (ULN); ALT and AST < 2.5 × ULN; in case of liver metastases, ALT and AST < 5 × ULN; Cr ≤1.5×ULN or creatinine clearance (CCr) ≥60ml/min; Coagulation function is good, INR and PT ≤1.5 times ULN; if the subject is receiving anticoagulant treatment, PT should be within the prescribed range of use of anticoagulant drugs; Women of child-bearing age should agree to take contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study and within 6 months after the study; non-breast-feeding patients whose serum or urinary pregnancy test should be negative; male patients should agree to take contraceptive measures during the study and within 6 months after the study. Patients are voluntarily enrolled into the study, sign the informed consent form and have good compliance. Exclusion Criteria: Subjects with active CNS metastases are excluded. Non-small cell lung cancer. With obvious hemorrhage symptom Patients with many factors affecting oral medication, such as dysphagia, gastrointestinal resection, chronic diarrhea and intestinal obstruction. Combined with other tumors at the time of initial diagnosis. Patients who have previously participated in other clinical trials and have not yet terminated the trial. Patients who have acute infection that difficult to control.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib plus etoposide and carboplatin<br>Etoposide and carboplatin plus anlotinib for 4 cycles and anlotinib as maintenance therapy | Drug: Anlotinib hydrochloride<br>* anlotinib 10 mg/day orally (from days 1 to 14 in a 21-day cycle)<br>* Other names: anlotinib;Drug: Etoposide<br>* 100mg/m2 iv on days 1-3 every 21 days for 4 cycles<br>* Other names: VP-16;Drug: Carboplatin<br>* AUC 5 iv on day 1 every 21 days for 4 cycles<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Time from enrollment to progression or death | Time from randomization to progression, assessed 9-11 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Patients who were assessed as partial response or complete response | 6-9 weeks | 
| OS | Time from enrollment to death of any cause | 13-15 months | 
| DCR | Patients who were assessed as partial response, complete response or stable disease | 6-9 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SCLC, Anlotinib