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
Conditions
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.
Interventions
DRUGDexamethasone
Given PO BID
DEVICEDevice for PET
Undergo 18F-FLT PET scan
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDUREPositron Emission Tomography
Undergo 18F-FLT PET scan
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Tumor SUVmax Assessed by 18F-FLT PET Imaging | Baseline to day 9 | The primary endpoint is reported with mean and standard deviation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fold Change in Senescence Marker Gro-alpha | Baseline to day 9 | Fold change in senescence marker Gro-alpha from scan 1 to scan 3 |
| Fold Change in Senescence Marker Gro-beta | Baseline to day 9 | Fold change in senescence marker Gro-alpha from scan 1 to scan 3 |
| Fold Change in Senescence Marker MCP-1 | Baseline to day 9 | Fold change in senescence marker Gro-alpha from scan 1 to scan 3 |
| Tumor Glucocorticoid Receptor Alpha Expression | Baseline | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Dexamethasone, 18F-FLT 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.
Dexamethasone: Given PO BID
Device for PET: Undergo 18F-FLT PET scan
Laboratory Biomarker Analysis: Correlative studies
Positron Emission Tomography: Undergo 18F-FLT PET scan | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Dexamethasone, 18F-FLT PET) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 63 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Change in Tumor SUVmax Assessed by 18F-FLT PET Imaging
The primary endpoint is reported with mean and standard deviation
Time frame: Baseline to day 9
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Dexamethasone, 18F-FLT PET) | Change in Tumor SUVmax Assessed by 18F-FLT PET Imaging | -0.39 SUVmax | Standard Deviation 0.39 |
p-value: 0.087t-test, 2 sided
Secondary
Fold Change in Senescence Marker Gro-alpha
Fold change in senescence marker Gro-alpha from scan 1 to scan 3
Time frame: Baseline to day 9
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Dexamethasone, 18F-FLT PET) | Fold Change in Senescence Marker Gro-alpha | 2.46 fold change is unitless | Standard Deviation 0.35 |
Secondary
Fold Change in Senescence Marker Gro-beta
Fold change in senescence marker Gro-alpha from scan 1 to scan 3
Time frame: Baseline to day 9
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Dexamethasone, 18F-FLT PET) | Fold Change in Senescence Marker Gro-beta | 8.34 fold change is unitless | Standard Deviation 7.05 |
Secondary
Fold Change in Senescence Marker MCP-1
Fold change in senescence marker Gro-alpha from scan 1 to scan 3
Time frame: Baseline to day 9
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Dexamethasone, 18F-FLT PET) | Fold Change in Senescence Marker MCP-1 | 14.8 fold change is unitless | Standard Deviation 17.37 |
Secondary
Tumor Glucocorticoid Receptor Alpha Expression
Time frame: Baseline
Population: Needle biopsies were collected for routine care. There was not enough tissue left after the routine care analyses to perform the exploratory analysis specified in this endpoint.