Apatinib in the Treatment of Advanced Non-squamous Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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Apatinib is a new kind of Vascular endothelial growth factor receptor(VEGFR) tyrosine kinase inhibitors (TKIs). The investigators have finished the preclinical and phase I and phase II clinical study for apatinib and found its satisfactory anti-tumor activity and tolerated toxicities. A disease-control rate of 75% was found in lung cancer patients. In the present phase III trial, the investigators will further evaluate the efficacy and toxicities of apatinib in the treatment of advanced non-squamous non-small cell lung cancer.

Official Title
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Apatinib in the Treatment of Advanced Non-squamous Non-small Cell Lung Cancer:a Randomised, Double-blind, Placebo-controlled, Multicentre Phase III Study

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: apatinib
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 to 70 years of age Documented pathological evidence of advanced non-squamous non-small cell lung cancer with measurable lesions Failure of epidermal-growth-factor receptor (EGFR) TKIs target treatment and second-line or more regimens of chemotherapy Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 1 Patients had to have recovered from any toxic effects of therapy Patients with brain/meninges metastasis should keep stable disease for 2 months before randomisation Adequate hematologic and biochemical values were required Exclusion Criteria: Presence of small-cell lung cancer alone or with NSCLC Pregnant or breast-feeding women Severe or uncontrolled systemic disease such as clinically significant hypertension(systolic pressure > 140 mmHg，diastolic pressure > 90 mmHg), cardiac ischemia and infarction, ventricular arrhythmias(QT ≥ 440ms) and grade 1 cardiac insufficiency Difficulties in taking pills (inability to swallow tablets,GI tract resection, chronic bacillary diarrhea and intestinal obstruction) Coagulation disfunction,hemorrhagic tendency or receiving anticoagulant therapy ≥ CTCAE 2 pneumorrhagia or ≥ CTCAE 3 hemorrhage in other organs within 4 weeks Bone fracture or wounds that was not cured for a long time Arterial thrombus or phlebothrombosis within 6 months and taking anticoagulant agents Mental diseases and psychotropic substances abuse Previous treatment with an experimental agent within 4 weeks Previous treatment with VEGFR、platelet derived growth factor receptor(PDGFR) TKIS Other coexisting malignant disease (apart from basal-cell carcinoma and carcinoma in situ of uterine cervix)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Apatinib<br>750 mg，po，QD； 28 days every cycle | Drug: apatinib<br>* 750 mg，po，QD； 28 days every cycle<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* po，QD； 28 days every cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | Progression-free survival as the time from randomization to documented disease progression according to response evaluation criteria in solid tumors (RECIST) or death. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | ORR was the percentage of patients who got partial or complete response | 24 months | 
| Overall Survival(OS) | OS was determined from date of enrollment until death or the date the patient was recorded alive of last follow-up | 24 months | 
| Toxicity | Adverse events (AEs) were recorded, graded for toxicity using the NCI-CTC, and assessed by the investigator for any relationship with treatment. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apatinib, Non-small Cell Lung Cancer, VEGFR TKIs