Transarterial Chemoembolization for the Treatment of Lung Cancer

Study Overview
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Brief Summary
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This phase II trial evaluates how well transarterial chemoembolization (TACE) works for treating patients with non-small cell lung cancer. TACE is a minimally invasive procedure that involves injecting chemotherapy directly into an artery that supplies blood to tumors, and then blocking off the blood supply to the tumors. Mitomycin (chemotherapy), Lipiodol (drug carrier), and Embospheres (small plastic beads that block off the artery) are injected into the tumor-feeding artery. This traps the chemotherapy inside the tumor and also cuts off the tumor's blood supply. As a result, the tumor is exposed to a high dose of chemotherapy, and is also deprived of nutrients and oxygen. TACE can be effective at controlling or stopping the growth of lung tumors.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine safety and efficacy (local progression free survival) of chemoembolization of lung cancer that is chemorefractory, unresectable, and unablatable. OUTLINE: Patients receive lung chemoembolization using Lipiodol, mitomycin, and Embospheres. Response to treatment is evaluated on computed tomography (CT) scans.

Official Title
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Phase II Trial of Lung Chemoembolization

Conditions
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Lung Non-Small Cell Carcinoma, Mediastinal Neoplasm, Pleural Neoplasm

Intervention / Treatment
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* Procedure: Computed Tomography
* Drug: Ethiodized Oil
* Drug: Mitomycin
* Procedure: Transarterial Chemoembolization
* Device: Tris-acryl Gelatin Microspheres


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-small cell lung cancer (any stage), with lung, endobronchial, pleural, or mediastinal tumors that are progressing on systemic therapy (or the patient cannot tolerate systemic therapy), and that are not amenable to resection, thermal ablation, or ablative radiation therapy Lung-dominant disease (majority of active tumor volume is in the chest) At least 18 years old Exclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status > 2 Oxygen saturation < 92% on room air Forced expiratory volume in 1 second (FEV1) < 60% No measurable treatable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (for example, unable to measure tumor size on CT, or lung nodules are all < 1 cm) Life expectancy < 6 months Pulmonary hypertension (diagnosed or suspected on echocardiography, CT, magnetic resonance imaging [MRI], or direct pressure measurement) Recent pulmonary embolism (within 3 months) Pulmonary arteriovenous malformation Active lung infection (pneumonia, empyema, or lung abscess requiring therapy within 1 month) Symptomatic heart failure (American College of Cardiology [ACC]/American Heart Association [AHA] stage C or D) Left bundle branch block (contraindication to pulmonary angiography) Renal failure (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m^2) Pregnancy or intent to become pregnant Breast feeding Altered mental status that would interfere with consent or follow-up Platelets < 50,000 (after transfusion, if needed) International normalized ratio (INR) > 2 (after transfusion, if needed) Hemoglobin < 7 (after transfusion, if needed) Hyperthyroidism or history of hyperthyroidism, including subclinical hyperthyroidism (contraindication to lipiodol) Planned radioactive iodine imaging or therapy (contraindication to lipiodol) Allergy to lipiodol or mitomycin Allergy to iodinated contrast that cannot be treated with steroid / diphenhydramine premedication Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, or that would affect subject safety

Ages Eligible for Study
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Minimum Age: 18 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: Lung chemoembolization<br>Patients receive lipiodol intra-arterially (IA), mitomycin IA, and embospheres IA and undergo TACE on study. Patients also undergo angiography and computed tomography (CT) at baseline and follow up. | Procedure: Computed Tomography<br>* Undergo CT<br>* Other names: tomography;Drug: Ethiodized Oil<br>* Given IA<br>* Other names: Lipiodol;Drug: Mitomycin<br>* Given IA<br>* Other names: NCI-C04706;Procedure: Transarterial Chemoembolization<br>* Undergo TACE<br>* Other names: TACE;Device: Tris-acryl Gelatin Microspheres<br>* Given IA<br>* Other names: Trisacryl Gelatin Microspheres;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local progression free survival | Progression is determined using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. criteria, compared to the scan immediately prior to treatment of that territory, using the 2 largest measurable lesions per treated territory. Local progression-free survival will be estimated using the Kaplan-Meier method. | Time from the initial transarterial chemoembolization (TACE) treatment to progression in a completely treated territory (or touching the border of a completely treated area), or death from any cause, assessed at 6 months | 
| Incidence of adverse events | Complications will be classified using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The rate of complications can be estimated with a standard error of less than 10%. Further, any complication that occurs with a 10% incidence will be observed with greater than 95% probability. | Up to 3 months after the last chemoembolization procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (best response) | Evaluated on a per-treatment basis, using RECIST version 1.1 criteria. | Within 3 months of treatment | 
| Overall survival | Will be estimated using the Kaplan-Meier method. | Up to 9 months | 
| Progression-free survival | Will be estimated using the Kaplan-Meier method. | Up to 9 months | 
| Bronchial versus pulmonary artery blood supply | Percentage of treatments where target tumors were supplied by bronchial artery, non-bronchial systemic artery, or pulmonary artery, based on catheter angiography. Confidence intervals of proportions will be estimated using the equal-tailed Jeffreys prior interval. | Up to 9 months | 
| Lipiodol retention in treated tumors | Correlation between lipiodol retention and change in tumor size will be evaluated using Spearman's rank correlation coefficient (rho) and Spearman's test. | 4-6 weeks post-procedure | 
| Growth of TACE targeted lesions versus non-TACE targeted lesions | Percentage change in size (largest diameter) of the largest treated, compared to the largest untreated tumor will be evaluated using the Wilcoxon signed-rank test. | 4-6 weeks post-procedure |