The Efficacy and Safety of Apatinib in Heavily Pretreated Advanced Non-squamous Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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The development of anti-angiogenesis drugs has led to renewed enthusiasm in lung cancer treatments. Apatinib, also known as YN968D1, is a tyrosine kinase inhibitor which selectively inhibits the vascular endothelial growth factor receptor-2 (VEGFR-2) and also represents mild inhibition to PDGFR, c-Kit and c-src tyrosine kinases. It is an orally bioavailable, small molecule agent which is thought to inhibit VEGF-mediated endothelial cell migration and proliferation thus blocking blood vessel formation in tumor tissues. Previous studies have identified that apatinib was well tolerated at doses below 750mg daily. In phase I/II study, investigators reported an objective response rate of 68%. In a phase III trial conducted in advanced pretreated gastric cancer, the median overall survival was significantly prolonged in the apatinib group compared with placebo group. Thus, in this trial, the investigators aim to investigate the efficacy and safety of apatinib in previously treated advanced non-squamous non-small cell lung cancer.

Detailed Description
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Observing the efficacy and safety of apatinib in heavily treated non-squamous non-small cell lung cancer. Primary Outcome Measure: Objective Response Rate Secondary Outcome Measures: Progression free survival, overall survival, Side effects, Quality Of Life

Official Title
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Single Arm Phase II Clinical Trial to Investigate the Efficacy and Safety of Apatinib as a Single Agent in Advanced NSCLC Who Failed to at Least Two Lines Systemic Treatment, or Were Not Amendable to Receive the Second-line Standard Therapy

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: apatinib single agent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obtain of informed consent. Aged 18 years and over. Histologically or cytologically confirmed non-squamous non-small cell lung cancer. World Health Organization (WHO) performance status (PS) of 0 to 2. Measurable lesions as defined by RECIST criteria. Life expectancy ≥12 weeks. Progressed after at least two lines systemic treatment, or were not amendable to receive the current standard therapy 7. Organ functions normal, as defined below, within two weeks of randomization: Hb≥90g/L Absolute neutrophils count(ANC)≥1.5×109/L Platelets≥80×109/L Serum bilirubin≤2×ULN; Aspartate transaminase(AST) and alanine transaminase (ALT)≤2.5×ULN(≤5×ULN if liver metastases) Creatinine clearance≥45ml/min or Cr≤1.25×ULN 8. Females of child-bearing potential must have negative serum pregnancy test. Sexually active males and females (of childbearing potential) willing to practice contraception during the study. Exclusion Criteria: Squamous carcinoma (including adeno-squamous carcinoma), small cell lung cancer. Newly diagnosed Central Nervous System (CNS) metastases that have not yet been definitively treated with surgery and/or radiation. Tumor invade big vessels or close to big vessels (less than 5mm) Obvious cavity or necrosis formed in the tumor Uncontrolled hypertension Myocardial ischemia or infarction more than stage II, cardiac insufficiency. Abnormal coagulation (INR>1.5 or PT>ULN+4, or APTT>1.5 ULN), bleeding tendency or receiving coagulation therapy Hemoptysis, more than 2.5ml daily Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous thrombosis. Unhealed bone fracture or wound for long time Received big surgery, had bone fracture or ulcer in 4 weeks. Urine protein≥++, or urine protein in 24 hours≥1.0g Pregnant or lactating woman.

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: apatinib single agent<br>apatinib, single agent, 500mg or 750mg Qd po, continue until disease progression | Drug: apatinib single agent<br>* For those heavily treated non-squamous non-small cell lung cancer, treat with apatinib single agent, 500mg or 750mg Qd, p.o based on the status of patient, continue until disease progression, dose reduction was admitted<br>* Other names: YN968D1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | To evaluate Objective response rate every 6-8 weeks after the initiation of apatinib. | tumor assessment every 2 cycles after the initiation of apatinib，up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | PFS is evaluated in 24 months since the treatment began | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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apatinib, NSCLC, safety, efficacy