Study of Anlotinib in Patients With Advanced Non-small Cell Lung Cancer（ALTER0303）

Study Overview
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Brief Summary
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Evaluate the efficacy and safety of Anlotinib as the 3-line treatment of patients with advanced non-small lung cancer, with placebo control.

Detailed Description
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Anlotinib (AL3818) is a kind of innovative medicines approved by State Food and Drug Administration（SFDA:2011L00661） which was researched by Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd. Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR1、VEGFR2、VEGFR3、FGFR1/2/3、PDGFRa/β c-Kit and MET.

Official Title
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A Registered Randomized, Double-Blind, Placebo-Controlled (2:1), Multi-Centered Clinical Trial of Anlotinib as a Treatment for Advanced Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Anlotinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent Diagnosed with advanced NSCLC (phase IIIB/IV) through pathology, with measurable nidus(using RECIST 1.1) at least two systematic chemotherapy with upwards of 3-line treatments or cannot suffer Patients must provide detectable specimen (from tumor tissue or hydrothorax) before participating, who negative in EGFR&ALK can participate or who positive in EGFR&ALK, have or have not drug tolerance after the treatment with relative targeted drugs ECOG PS：0-1,Expected Survival Time: Over 3 months main organs function is normal The woman patients of childbearing age who must agree to take contraceptive methods (e.g. intrauterine device, contraceptive pill or condom) during the research and within another 6 months after it; who are not in the lactation period and examined as negative in blood serum test or urine pregnancy test within 7 days before the research; The man patients who must agree to take contraceptive methods during the research and within another 6 months after it Exclusion Criteria: have used Anlotinib before Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer) examined as positive in EGFR&ALK mutation detection and never take the treatment of TKIs central lung squamous carcinoma along with cavum, or non-small cell lung cancer along with hemoptysis (>50ml/day) other kinds of malignancies within 5 years or for now plan to take systemic anti-tumor therapy within 4 weeks before grouping or during the medicine-taking period of this research, including Cytotoxic Therapy, Signal Transduction Inhibitor, and Immunotherapy (or who use Mitomycin C within 6 weeks before taking the treatment with experimental drug); The patients who have already taken Extended Field Radiotherapy (EF-RT) within 4 weeks before grouping or Limited Field Radiotherapy with proposed assessment of nidus within 2 weeks before grouping have got non remissive toxic reactions derived from previous therapies, which is over level 1 in CTC AE (4.0), alopecia NOT included with kinds of factors which affect oral medicine (e.g. failing to swallow, gastrointestinal tract getting resected, chronic diarrhea and ileus) pleural effusion or ascites, resulting in respiratory syndrome (≥CTC AE level 2) symptoms of brain metastases cannot be controlled and treated within less than 2 months get any severe diseases or the ones that cannot be controlled take major surgical treatments, open biopsy, or get overt traumatic injury within 28 days before grouping have any habitus or medical history of hemorrhage, however severe it is; the patients who have non healing wounds, ulcer or fracture after any events with hemorrhage or bleeding (≥CTCAE level 3) get arterial/venous thrombosis within 6 months, such as cerebrovascular accidents (including temporary ischemic stoke), deevenous thrombosis, and pulmonary embolism ever abuse psychiatric drugs and cannot abstain or who are diagnosed with mental disorder have participated in other clinical trials of anti-tumor medicine within 4 weeks diagnosed with disease which will severely endanger the security of patients or influence the completion of this research.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib<br>Anlotinib p.o, qd and it should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent | Drug: Anlotinib<br>* Basic dosage, take once when limosis in the morning. If patients cannot suffer from AEs, they can get declined dosage.<br>* Other names: AL3818;|
| Placebo Comparator: Placebo<br>Placebo p.o, qd and it should be continued until disease progress or patients withdraw consent | Drug: Placebo<br>* Basic dosage, take once when limosis in the morning.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | From randomization until death (up to 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress free survival (PFS) |  | each 42 days up to PD or death(up to 24 months) | 
| Objective Response Rate (ORR) |  | each 42 days up to intolerance the toxicity or PD (up to 24 months) | 
| Disease Control Rate (DCR) |  | each 42 days up to intolerance the toxicity or PD (up to 24 months) | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability |  | Until 30 day safety follow-up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anlotinib, Cancer, NSCLC, Non-small Cell Lung Cancer