Study of Apatinib in RET Fusion Positive Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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RET fusions are present in 1% to 2% of unselected population of non-small cell lung cancer (NSCLC). Existing US Food and Drug Administration-approved inhibitors of RET tyrosine kinase show promising therapeutic effects in a non-small cell lung cancer patients. Apatinib is an oral multi-kinase inhibitors including RET fusions. This study is designed to evaluate the safety and tolerability of Apatinib in patients with RET fusion positive advanced NSCLC.

Detailed Description
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To observe objective response rate (ORR) of apatinib in RET fusion positive pre-treated advanced NSCLC. To observe Progression free survival （PFS）. To assess the overall survival (OS). To assess safety and tolerability. To evaluate quality of life. To explore the relationship between biomarkers and the toxicity/efficacy of apatinib.

Official Title
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A Phase II Clinical Trial to Investigate Efficacy and Safety of Apatinib as a Single Agent in RET-fusion Gene Positive Non-small Cell Lung Cancer Who Failed to Previous Treatment.

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Apatinib single agent arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 and ≤80 years. ECOG performance status of 0 to 1. Life expectancy of more than 12 weeks. At least one measurable lesion exists.(RECIST 1.1) Histologically or cytologic confirmed RET fusion positive advanced Non-small cell lung cancer who failed to prior therapies. Required laboratory values including following parameters: ANC: ≥ 1.5 x 10^9/L, Platelet count: ≥ 80 x 10^9/L, Hemoglobin: ≥ 90 g/L, Total bilirubin: ≤ 1.5 x upper limit of normal, ULN, ALT and AST: ≤ 1.5 x ULN, BUN and creatine clearance rate: ≥ 50 mL/min LVEF: ≥ 50% QTcF: < 470 ms Signed informed consent Females of child-bearing potential must have negative serum pregnancy test. Sexually active male and those having childbearing potential must practice contraception during the study. Exclusion Criteria: Squamous carcinoma (including adeno-squamous carcinoma), small cell lung cancer Subjects with third space fluid that can not be controled by drainage or other methods. Obvious cavity or necrosis formed in the tumor Uncontrolled hypertension Hymoptysis, more than 2.5ml daily Thrombosis in 12 months, including pulmonary thrombosis, stroke, or deep venous thrombosis 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 Receiving any other antitumor therapy. Known history of hypersensitivity to apatinib or any of it components.

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 arm<br>Apatinib, single agent, 750mg once daily p.o until disease progression | Drug: Apatinib single agent arm<br>* For RET-fusion positive advanced NSCLC patients who failed to previous treatment,treat with apatinib, single agent, 750mg once daily, p.o until disease progression<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 (ORR) | To evaluate ORR every 6-8 weeks after initiation of apatinib | change from baseline in tumor size every 6-8 weeks after the initiation of apatinib, up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is evaluated in 24 months since the treatment began | 24 months | 
| overall survival (OS) | evaluated in the 24th month since the treatment began | 24 months | 
| Safety and Tolerability as measured by adverse events | Number of Participants with treatment related Adverse Events as Assessed by CTCAE v4.0 | 24 months | 
| quality of life (QOL, measured by questionnaire) | Change from baseline in Pain on the 11 point short pain scale (SPS-11) | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apatinib, RET, gene fusion, Non-small Cell Lung Cancer