Efficacy and Safety of DEB-BACE With Sequential Arotinib and Tirelizumab in the Treatment of Advanced NSCLC

Study Overview
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Brief Summary
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This is a prospective, open-labelled study to evaluate the efficacy and safety of arterial infusion chemotherapy combined with drug loaded microspheres embolization with sequential arotinib and tirelizumab in the treatment of advanced NSCLC. The progression-free-survival (PFS) will be evaluated as the primary endpoints.

Official Title
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Efficacy and Safety of Bronchial Arterial Infusion Chemotherapy Combined With Drug Loaded Microspheres Embolization With Sequential Arotinib and Tirelizumab in the Treatment of Advanced NSCLC

Conditions
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Carcinoma, Non-Small Cell Lung

Intervention / Treatment
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* Drug: sequential DEB-BACE and Arotinib and Tirelizumab
* Drug: DEB-BACE alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has fully understood and voluntarily signed an written Informed Consent and agreed to follow the research plan treatment and visiting plan; Aged >=18 years, <= 85 years; Patients with NSCLC diagnosed by imaging and histopathology; TNM stage was III-IV; Initial diagnosis, failure of first-line treatment, refusal or inability to perform routine treatment (surgery, radiotherapy and chemotherapy); Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Expected survival period ≥ 3 months. Exclusion Criteria: Known hypersensitivity to any of the study drugs or excipients; Hypertension that is not controlled by the drug; International normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 × ULN; WBC count < 3000 /mm3; Platlet count < 50000 /mm3; Poorly controlled diabetes before enrollment; Clinically significant electrolyte abnormalities judged by researchers; Patients with obvious evidence of bleeding tendency or medical history of hematochezia within 3 months before enrollment; Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe / unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; Congestive heart failure, New York Heart Association (NYHA) grade > 2; ventricular arrhythmia requiring drug treatment; LVEF (left ventricular ejection fraction) < 50%; Active infection or serious infection that is not controlled by drug; History of clinically significant hepatic disease (ALT and/or AST >5 times the upper normal limit); Women who are pregnant or lactating; Urinary protein ≥ ++, and the 24-hour urine protein quantification is greater than 1.0g; Have any other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other conditions, which according to the judgment of the investigator, it is reasonable to suspect that the patient is not suitable for the use of the study drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sequential DEB-BACE and Arotinib and Tirelizumab<br>First treatment. Only infusion chemotherapy (THP + Nedaplatin + Letitrexed), THP 20   30mg/m2, Nedaplatin 40mg/m2, Letitrexed 3mg/m2. Second treatment. After infusion chemotherapy, Callispheres microspheres is used for embolization: Callispheres microspheres (300-500 μ m) 1tube was loaded and adsorbed THP (40   600mg/m2) End point of embolization: stagnation of blood flow in tumor feeding artery. The third treatment. Arotinib, 8-12mg, oral (stop oral for 1W every 3W).Tirelizumab, 200mg, intravenous drip (every 3W). | Drug: sequential DEB-BACE and Arotinib and Tirelizumab<br>* DEB-BACE+Arotinib + Tirelizumab<br>|
| Active Comparator: DEB-BACE alone<br>First treatment. Only infusion chemotherapy (THP + Nedaplatin + Letitrexed), THP 20   30mg/m2, Nedaplatin 40mg/m2, Letitrexed 3mg/m2. Second treatment. After infusion chemotherapy, Callispheres microspheres is used for embolization: Callispheres microspheres (300-500 μ m) 1tube was loaded and adsorbed THP (40   600mg/m2) End point of embolization: stagnation of blood flow in tumor feeding artery. | Drug: DEB-BACE alone<br>* DEB-BACE alone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS was defined as the time from recruitment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | ORR is defined as the percentages of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria | up to 3 years | 
| Overall survival (OS) | The time from recruitment to death due to any cause. | up to 3 years |