A Metal Bare Stent With 125 Iodine （125I）Seeds for the Treatment of Malignant Central Airway Stenosis

Study Overview
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Brief Summary
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Malignant central airway stenosis caused by primary or metastatic malignant tumor may lead to dyspnea even death of patients.With the rapid development of interventional pulmonology, bronchoscopic therapy has become the main treatment for malignant central airway stenosis. Metal stent implantation in airway can quickly relieve respiratory obstruction and improve quality of life.However, the tumor tissue can continue to grow into metal stent and obstruct airway again. This is the shortcoming of metal bare stents, which often need further treatment to keep airway open, including ablation, laser, cryotherapy, external radiotherapy or systemic anti-tumor drug therapy.Metal stent implantation combined with external radiotherapy can effectively reduce the incidence of airway restenosis.However, complications of external radiotherapy are high, including bone marrow suppression, radioactive pneumonia, radioactive esophagitis, myocardial injury and tracheoesophageal fistula, of which may cause serious consequences and even cause death of the patient.125I radioactive seeds have been one of the mature radioactive interventional therapy, which release X rays, and γ rays. Because of the short radioactive distance, 125I seeds can destruct tumor cells in tumor site and promote apoptosis and necrosis of tumor cells around the obstruction of the airway, meanwhile cause little damage to the surrounding normal tissues. Some studies showed that 125I seed implantation of lung tumor lesions achieved good short-term results.Therefore, the investigators hypothesize that 125I seeds fixed on the metal bare stent can not only improve the patient's breathing difficulties, but also play a role in killing tumor cells. At present, there have been reports of related clinical cases and monocentric control studies of malignant central airway stenosis treated with the implantation of metal stent with 125I seeds, but there is a lack of multicentric clinical studies with large samples.

Detailed Description
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It is an open, multicentric randomized controlled clinical trial conducted in China, and plan to recruiting 200 patients who suffer malignant central airway stenosis. To evaluate the efficacy and safety of metal stent with 125I seeds group and metal bare stent group in the treatment of malignant central airway stenosis, follow-up should be done within 1 week, 1 month, and 3 months after the first treatment, followed by every 3 months. The contents include review of bronchoscopy and chest CT, blood routine, immune indicators (IgA, immunoglobulin M（Ig M）, IgG), evaluation of general conditions. The patients of the first group need emission-computed tomography（ECT） imaging or positron emission tomography-computed tomography （PET-CT） examination within 1 month. If the patient has severe dyspnea, emergency bronchoscopy should be performed .

Official Title
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The Efficacy and Safety of a Metal Bare Stent With 125I Seeds for the Treatment of Malignant Central Airway Compared to a Metal Bare Stent: A Multicentric Randomized Controlled Study.

Conditions
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Malignant Airway Obstruction

Intervention / Treatment
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* Procedure: stent implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age range: 18-75 years old, male or female who is not pregnant Comply with the diagnosis of malignant central airway stenosis, and undergo chest CT or bronchoscopy to confirm that the stenosis degree is above 50% and need to be implanted with airway metal stent; or the patient has obvious dyspnea due to airway stenosis, obstructive pneumonia Subjects voluntarily joined the study and signed informed consent, with good compliance and follow-up. Unable or refused surgery Unable or refused external radiation therapy Unable or refuse systemic tumor-related drugs therapy within 3 months Exclusion Criteria: The distal end of the stenosis is unpredictable, and the stent treatment may not be satisfactory; Severe arrhythmia, acute myocardial ischemia, uncontrollable hypertensive crisis; Severe coagulopathy Severe organ dysfunction (except respiratory insufficiency) Allergic to anesthetics Airway fistula lesions The narrow lesion involves 2cm inside the glottis History of extrathoracic radiation therapy in the past 6 months Severe myelosuppression

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A metal bare stent with 125I seeds<br>125I seeds fixed on the metal bare stent, then stent implantation | Procedure: stent implantation<br>* stent implantation<br>|
| Other: A metal bare stent<br>A metal bare stent implantation | Procedure: stent implantation<br>* stent implantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| stenosis grade | Stenosis grade was classified as 5 grades on the cross-sectional CT imaging area: grade 0 = non-appreciable stenosis; grade 1, 2, 3, and 4 = 25, 50, 75, and 90% decrease in area, respectively; grade 5 = complete obstruction | the first month after stent implantation | 
| stenosis grade | Stenosis grade was classified as 5 grades on the cross-sectional CT imaging area: grade 0 = non-appreciable stenosis; grade 1, 2, 3, and 4 = 25, 50, 75, and 90% decrease in area, respectively; grade 5 = complete obstruction | the third month after stent implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival （OS） | overall survival | From randomization until death （up to 24 months） | 
| technical success | successful implantation of the stent across the stricture with appropriate positioning of the stent and full expansion | one week after stent implantation | 
| complications and side effects | Possible radiation related complications included neutropenia, decrease in IgA, IgG, and IgM, and leakage of radioactive seeds.Neutropenia was defined as a total white blood cell count b4000/mm3 in the plasma. The leakage of radioactive seeds was defined as the detection of non-target radioactive source verified by radiography | From randomization until death （up to 24 months） | 
| tumor growth rate | the size of tumor assessed by CT after stent implantation | From randomization until death （up to 24 months） | 
| the time of emergency endoscopic treatment | record the time of emergency endoscopic treatment for the recurrent severe dyspnea of patient | From randomization until death （up to 24 months） |