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

Not Applicable

Active, not recruiting

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

Interventions: Drug: Dexamethasone
Device: Device for PET
Other: Laboratory Biomarker Analysis
Procedure: Positron Emission Tomography

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Treatment (dexamethasone, 18F-FLT PET)	Laboratory Biomarker Analysis	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.
Treatment (dexamethasone, 18F-FLT PET)	Positron Emission Tomography	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.
Treatment (dexamethasone, 18F-FLT PET)	Device for PET	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.
Treatment (dexamethasone, 18F-FLT PET)	Dexamethasone	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in senescence markers in circulating tumor cells	Baseline to day 9
Change in serum dexamethasone concentration	Baseline to day 9
Tumor glucocorticoid receptor alpha expression	Baseline
Dexamethasone withdrawal as measured by changes in tumor FLT retention	Day 6-9	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.

Locations (1): Wayne State University/Karmanos Cancer Institute
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Detroit, Michigan, United States