A Study of Apatinib Plus EGFR-TKI as First Line Treatment in Patients With Non-squamous NSCLC Harboring EGFR Mutations

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of apatinib plus EGFR-TKI as first line treatment in patients with non-squamous NSCLC harboring EGFR mutation.

Official Title
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A Study of Apatinib Plus EGFR-TKI as First Line Treatment in Patients With Non-squamous NSCLC Harboring EGFR Mutations

Conditions
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NSCLC

Intervention / Treatment
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* Drug: Apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age:18 to 75 years old (man or female); Pathologically diagnosed with non-squamous NSCLC; Imageology diagnosed with locally advanced/metastatic or recurrent (stage ⅢB - IV); Histologically or cytologic confirmed，harboring an activating EGFR mutation (19del or 21 L858R); None previous chemotherapy or targeted therapy.（NOTE: neoadjuvant and adjuvant therapy is allowed）; At least one measurable lesion (measuring≥10mm on spiral CT scan, satisfying the criteria in RECIST1.1)； Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; Major organ function has to meet the following criteria: HB≥90g/L； ANC≥1.5×109/L； PLT≥80×109/L； ALT and AST≤2.5ULN, but≤5ULN if the transferanse elevation is due to liver metastases; TBIL≤1.5ULN; Serum creatinine≤1.25ULN; Endogenous creatinine clearance rate>45 ml/min; Life expectancy greater than or equal to 3 months; Women of childbearing age must have contraceptive measures or have test pregnancy (serum or urine) enroll the study before 7 days, and the results must be negative, and take the methods of contraception during the test and the last to have drugs after 8 weeks. Men must be contraception or has sterilization surgery during the test and the last to have drugs after 8 weeks; Participants were willing to join in this study, and written informed consent, good adherence, cooperate with the follow-up. Exclusion Criteria: Have high blood pressure and antihypertensive drug treatment can not control (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg); Patients who suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female ≥ 470 ms). Grade III-IV cardiac insufficiency according to New York Heart Association(NYHA) criteria or echocardiography check: left ventricular ejection fraction (LVEF)<50%; Radiologically documented evidence of major blood vessel invasion or encasement by cancer; A variety of factors influencing oral drugs (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc); Patients with tendency of gastrointestinal bleeding, including the following: a local active ulcerative lesions, and defecate occult blood (++). Has melena and hematemesis in two months; Coagulant function abnormality (INR > 1.5 ULN, APTT > 1.5 ULN), with bleeding tendency; Patients with pregnant or planning a pregnancy; Patients with other malignant tumors within 5 years (except for the treated skin basal cell carcinoma and cervical carcinoma in situ); History of psychiatric drugs abuse and can't quit or patients with mental disorders; Less than 4 weeks from the last clinical trial; The researchers think inappropriate.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: apatinib<br>apatinib 500mg qd po plus Erlotinib 150mg qd po / apatinib 500mg qd po plus Icotinib 125mg tid po | Drug: Apatinib<br>* apatinib 500mg qd po plus Erlotinib 150mg qd po / apatinib 500mg qd po plus Icotinib 125mg tid po<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Baseline to measured date of progression or death from any cause | evaluated in two years since the treatment began | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Baseline to measured stable disease | tumor assessment every 8 weeks，up to two years | 
| Disease control rate (DCR) | Baseline to measured progressive disease | tumor assessment every 8 weeks，up to two years | 
| Overall survival (OS) | Baseline to measured date of death from any cause | the first day of treatment to death or last survival confirm date，up to two years | 
| Adverse events | throughout study | evaluated in the two years since the treatment began according to the Common Terminology Criteria for Adverse Events Version 4.0 |