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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-02899 | Other Identifier | CTRP (Clinical Trial Reporting Program) | |
| NA_00017885 | Other Identifier | Johns Hopkins Medicine IRBs | |
| J08134 | Other Identifier | JHU/Sidney Kimmel Comprehensive Cancer Center | |
| NCI 8340 | Other Identifier | CTEP | |
| N01CM00070 | U.S. NIH Grant/Contract | View source | |
| P30CA006973 | U.S. NIH Grant/Contract | View source |
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This study is being done to compare a special type of Positron Emission Tomography (PET) scan with CT scan in patients with surgically removable lung cancer to see which method is more useful in measuring a response to treatment. A PET scan uses small amounts of radioactive material injected into the blood to show the internal workings of the body. In this study, we will use two radioactive materials: 18F-FLT (referred to as FLT) and 18F-FDG (referred to as FDG). FDG is used routinely in the staging of lung cancer and is approved by the FDA for that purpose. FLT is used in the special type of PET scan being assessed by this study. In addition the study will assess the effects of the combination of docetaxel and cisplatin (chemotherapeutic drugs) on certain pathological characteristics of the tumor. The combination of docetaxel and cisplatin is approved by the Food and Drug Administration (FDA) for the treatment of advanced/metastatic NSCLC (non-small cell lung cancer). It is not approved for use in patients who have surgically removable NSCLC. In such cases cisplatin is used as a single drug therapy before surgery. The FDA is allowing the use of docetaxel along with cisplatin in this research study.
PRIMARY OBJECTIVES:
I. To determine if the absolute decrease measured in primary tumor 18 F-F-3'-fluoro-3'-deoxy-L-thymidine (FLT) uptake (standard uptake value [SUV] and influx constant [Ki]) between pre-treatment imaging and imaging after the first cycle of therapy differs in patients categorized as responders or non-responders based on Response Evaluation Criteria in Solid Tumors (RECIST) measured with computed tomography (CT) after the second cycle of therapy.
SECONDARY OBJECTIVES:
I. To determine if the absolute decrease measured in primary tumor FDG uptake (SUV) between pre-treatment imaging and imaging after the first cycle of therapy differs in patients categorized as responders or non-responders based on RECIST measured with CT after the second cycle of therapy.
II. To assess the effects of the combination of docetaxel and cisplatin on fractional tumor viability and proliferative fraction pre and post treatment and to correlate these with the PET SUV data for both tracers.
III. To assess the methylation status of the checkpoint with forkhead and ring finger domains gene (CHFR) gene from pre-treatment tumor biopsies and correlate methylation status post treatment with clinical and pathologic response.
OUTLINE:
Patients receive docetaxel intravenously (IV) and cisplatin IV on day 1 and dexamethasone orally (PO) twice daily (BID). Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo FDG PET/CT, FLT PET/CT, and thoracic CT at baseline and the end of courses 1 and 2 and then undergo surgery.
After completion of study treatment, patients are followed up for 4-6 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | Patients receive docetaxel IV and cisplatin IV on day 1. Treatment repeats every 3 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo FDG PET/CT, FLT PET/CT, and thoracic CT at baseline and the end of cycles 1 and 2 and then undergo surgery. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cisplatin | Drug | Given IV |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in 18F-Fluorothymidine (FLT) Uptake | Will be calculated by subtracting the uptake of the scan after the first cycle of chemotherapy from the uptake of the pre-treatment scan.. Change in FLT uptake will be measured using the maximum standard uptake value adjusted for lean body mass (SULmax), which is a measure of how much radiotracer (in this case FLT) is being consumed by cells. | Baseline and 3 weeks |
| Change in FLT Uptake | Will be calculated by subtracting the uptake of the scan after the second cycle of chemotherapy from the uptake of the pre-treatment scan. | Baseline and 6 weeks |
| Change in FLT Uptake in Responders and Non-responders | Unadjusted analysis will be performed utilizing students t-tests. If the data appears non-normal, the Wilcox on rank-sum test will be used rather than the t-test. Adjusted analysis will be performed utilizing logistic regression. | Baseline and 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in 18F-Fluorodeoxyglucose (FDG) Uptake | Will be calculated by subtracting the baseline FDG uptake from the post-cycle 2 uptake (as measured by SULmax). | Baseline and 6 weeks |
| Overall Response Rate Reported as a Proportion of the Total Number of Patients Who Received at Least One Cycle of Therapy Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Richard Wahl | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | 21287 | United States | ||
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Docetaxel, Cisplatin, Dexamethasone, and Surgery) | Patients receive docetaxel IV and cisplatin IV on day 1 and dexamethasone PO BID. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo FDG PET/CT, FLT PET/CT, and thoracic CT at baseline and the end of courses 1 and 2 and then undergo surgery. Cisplatin: Given IV Computed Tomography: Undergo FDG PET/CT, FLT PET/CT and thoracic CT Dexamethasone: Given PO Docetaxel: Given IV Fludeoxyglucose F-18: Undergo FDG PET/CT Fluorothymidine F-18: Undergo FLT PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo FDG PET/CT and FLT PET/CT Therapeutic Conventional Surgery: Undergo surgery |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| CT | Procedure | Undergo FDG PET/CT, FLT PET/CT and thoracic CT |
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| Docetaxel | Drug | Given IV |
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| FDG | Drug | Undergo FDG PET/CT |
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| FLT | Drug | Undergo FLT PET/CT |
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| PET/CT | Procedure | Undergo FDG PET/CT and FLT PET/CT |
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| Surgery | Procedure | Undergo surgery |
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RECIST version 1.1 was utilized for this outcome measure. A detailed description of RECIST 1.1 can be found here: Nishino M, Jackman DM, Hatabu H, Yeap BY, Cioffredi LA, Yap JT, et al. New Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for advanced non-small cell lung cancer: comparison with original RECIST and impact on assessment of tumor response to targeted therapy. AJR Am J Roentgenol 2010;195:W221-8. |
| Up to 6 weeks |
| Ohio State University Comprehensive Cancer Center |
| Columbus |
| Ohio |
| 43210 |
| United States |
| Completed Baseline Imaging |
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| Completed Post-Cycle 1 Imaging |
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| Completed Post-Cycle 2 FLT Imaging |
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| Completed Post-Cycle 2 FDG Imaging |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Docetaxel, Cisplatin, Dexamethasone, and Surgery) | Patients receive docetaxel IV and cisplatin IV on day 1 and dexamethasone PO BID. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo FDG PET/CT, FLT PET/CT, and thoracic CT at baseline and the end of courses 1 and 2 and then undergo surgery. Cisplatin: Given IV Computed Tomography: Undergo FDG PET/CT, FLT PET/CT and thoracic CT Dexamethasone: Given PO Docetaxel: Given IV Fludeoxyglucose F-18: Undergo FDG PET/CT Fluorothymidine F-18: Undergo FLT PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo FDG PET/CT and FLT PET/CT Therapeutic Conventional Surgery: Undergo surgery |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in 18F-Fluorothymidine (FLT) Uptake | Will be calculated by subtracting the uptake of the scan after the first cycle of chemotherapy from the uptake of the pre-treatment scan.. Change in FLT uptake will be measured using the maximum standard uptake value adjusted for lean body mass (SULmax), which is a measure of how much radiotracer (in this case FLT) is being consumed by cells. | Posted | Mean | Standard Deviation | SULmax | Baseline and 3 weeks |
|
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| ||||||||||||||||||||||||||
| Primary | Change in FLT Uptake | Will be calculated by subtracting the uptake of the scan after the second cycle of chemotherapy from the uptake of the pre-treatment scan. | Posted | Mean | Standard Deviation | SULmax | Baseline and 6 weeks |
|
| |||||||||||||||||||||||||||
| Primary | Change in FLT Uptake in Responders and Non-responders | Unadjusted analysis will be performed utilizing students t-tests. If the data appears non-normal, the Wilcox on rank-sum test will be used rather than the t-test. Adjusted analysis will be performed utilizing logistic regression. | Posted | Mean | Standard Deviation | SULmax | Baseline and 6 weeks |
|
| |||||||||||||||||||||||||||
| Secondary | Change in 18F-Fluorodeoxyglucose (FDG) Uptake | Will be calculated by subtracting the baseline FDG uptake from the post-cycle 2 uptake (as measured by SULmax). | Posted | Mean | Standard Deviation | SULmax | Baseline and 6 weeks |
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| Secondary | Overall Response Rate Reported as a Proportion of the Total Number of Patients Who Received at Least One Cycle of Therapy Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) | RECIST version 1.1 was utilized for this outcome measure. A detailed description of RECIST 1.1 can be found here: Nishino M, Jackman DM, Hatabu H, Yeap BY, Cioffredi LA, Yap JT, et al. New Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for advanced non-small cell lung cancer: comparison with original RECIST and impact on assessment of tumor response to targeted therapy. AJR Am J Roentgenol 2010;195:W221-8. | Posted | Number | percentage of participants | Up to 6 weeks |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment (Docetaxel, Cisplatin, Dexamethasone, and Surgery) | Patients receive docetaxel IV and cisplatin IV on day 1 and dexamethasone PO BID. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo FDG PET/CT, FLT PET/CT, and thoracic CT at baseline and the end of courses 1 and 2 and then undergo surgery. Cisplatin: Given IV Computed Tomography: Undergo FDG PET/CT, FLT PET/CT and thoracic CT Dexamethasone: Given PO Docetaxel: Given IV Fludeoxyglucose F-18: Undergo FDG PET/CT Fluorothymidine F-18: Undergo FLT PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo FDG PET/CT and FLT PET/CT Therapeutic Conventional Surgery: Undergo surgery | 4 | 9 | 0 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Neutropenic Fever | Immune system disorders | Non-systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John P Crandall | Washington University in St. Louis | (314) 747 - 5561 | jcrandall@wustl.edu |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D002945 | Cisplatin |
| C044245 | 1,2-diaminocyclohexaneplatinum II citrate |
| D010984 | Platinum |
| D000077143 | Docetaxel |
| D019788 | Fluorodeoxyglucose F18 |
| C002854 | alovudine |
| D009682 | Magnetic Resonance Spectroscopy |
| D013514 | Surgical Procedures, Operative |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D019216 | Metals, Heavy |
| D004602 | Elements |
| D028561 | Transition Elements |
| D008670 | Metals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D003847 | Deoxyglucose |
| D003837 | Deoxy Sugars |
| D002241 | Carbohydrates |
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
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