Dexamethasone Effects in Patients With Refractory Non-Small Cell Lung Cancer Using FLT Positron Emission Tomography

Study Overview
=================
Brief Summary
-----------------
This pilot research trial studies the effects of dexamethasone in patients with non-small cell lung cancer that has not responded after previous treatment. Drugs such as dexamethasone can affect how tumors grow and respond to treatments. Imaging tests, such as fluoro-L-thymidine (FLT) positron emission tomography , use a small amount of radioactive substance to show changes in tumor cells. Studying the effects of dexamethasone on lung tumors using FLT positron emission tomography may help doctors plan better treatments.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To evaluate the effect of dexamethasone (Dex) treatment in patients with relapsed non-small cell lung cancer (NSCLC) using 3'-fluorothymidine (FLT) positron emission tomography (PET) as measured by changes in tumor maximum standardized uptake value (SUVmax). SECONDARY OBJECTIVES: I. Assess the reversibility of Dex-mediated changes in tumor FLT retention following the withdrawal of Dex. II. Measure tumor Glucocorticoid Receptor alpha expression (GRα) from recent patient biopsy samples. III. Analyze blood samples obtained during imaging to determine serum Dex concentration and for senescence markers in circulating tumor cells. OUTLINE: Patients receive dexamethasone orally (PO) twice daily (BID) on days 1-5. Patients undergo 3 fluorothymidine F-18 (18F)-FLT PET scans. One scan within 7 days prior to the start of dexamethasone, one scan on day 3 after the 5th dose of dexamethasone, and one scan 6-9 days after the last dose of dexamethasone.

Official Title
-----------------
Study of the Effects of Dexamethasone on Non-Small Cell Lung Cancer Using [F-18] FLT for Imaging With Positron Emission Tomography (PET)

Conditions
-----------------
Recurrent Non-Small Cell Lung Carcinoma, Stage IIIA Non-Small Cell Lung Cancer, Stage IIIB Non-Small Cell Lung Cancer, Stage IV Non-Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Dexamethasone
* Device: Device for PET
* Other: Laboratory Biomarker Analysis
* Procedure: Positron Emission Tomography


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have histologically or cytologically proven advanced non-squamous NSCLC. Patients may have newly diagnosed recurrent progressive or refractory disease which may be localized or wide spread. No chemotherapy for at least 4 weeks and no radiation to the index lesion or clear progression in that lesion (greater than 20% increase in longest diameter). Life expectancy of greater than 4 weeks Absolute neutrophil count >= 1,000/mcL (measured within 2 weeks of registration) No history of human immunodeficiency virus (HIV) or active infections No history of diabetes No surgery in the last 2 weeks prior to study enrollment Has not received Dex or another corticosteroid in over 4 weeks prior to enrollment Ability to understand and the willingness to sign a written informed consent document Agreed to FLT-PET imaging and signed consent and eligible FLT-PET protocol 2006-127 Registered with the clinical trials office of the Karmanos Cancer Center/Wayne State University Exclusion Criteria: Patients must have measureable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques (computed tomography [CT], magnetic resonance [MR] or PET); lesions in the previously irradiated area can be considered as measureable lesions as long as there has been an increase of at least 10 mm when compared to measurements obtained after completion of radiation
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (dexamethasone, 18F-FLT PET)<br>Patients receive dexamethasone PO BID on days 1-5. Patients undergo 3 18F-FLT PET scans. One scan within 7 days prior to the start of dexamethasone, one scan on day 3 after the 5th dose of dexamethasone, and one scan 6-9 days after the last dose of dexamethasone. | Drug: Dexamethasone<br>* Given PO BID<br>* Other names: Visumetazone;Device: Device for PET<br>* Undergo 18F-FLT PET scan<br>* Other names: FLUOROTHYMIDINE F-18;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Positron Emission Tomography<br>* Undergo 18F-FLT PET scan<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tumor SUVmax assessed by 18F-FLT PET imaging | The primary analysis is one sample t-test for the change of SUVmax. | Baseline to day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in senescence markers in circulating tumor cells |  | Baseline to day 9 | 
| Change in serum dexamethasone concentration |  | Baseline to day 9 | 
| Dexamethasone withdrawal as measured by changes in tumor FLT retention | Secondary analyses will be carried out with descriptive statistics such as mean, SD, range. Correlation analysis will be descriptive. Spearman correlation coefficient will be calculated and scatter plot will be plotted. Subgroup analyses for dexamethasone withdrawal will be performed within the GRα high group. All subgroup analyses will be descriptive due to the expected small sample size. | Day 6-9 | 
| Tumor glucocorticoid receptor alpha expression |  | Baseline |