FDG-PET in Advanced Melanoma

Study Overview
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Brief Summary
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This clinical trial studies how well FDG-PET/CT measures early response in patients with stage III-IV melanoma who are receiving chemotherapy. Positron emission tomography (PET)/computed tomography (CT) uses a metabolic imaging radiotracer, [18F]fluorodeoxyglucose (FDG), which selectively accumulates in tumors. FDG-PET/CT of advanced melanoma before, during, and after treatment may improve methods for predicting which patients may benefit from therapy.

Detailed Description
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PRIMARY OBJECTIVES: I. To correlate treatment-induced changes in FDG uptake with changes in tumor size and progression-free survival (PFS) in patients receiving therapy for advanced melanoma. II. To correlate treatment-induced changes in FDG uptake with changes in the activity and/or expression of available molecular biomarkers from patients receiving therapy for advanced melanoma. OUTLINE: Patients undergo FDG-PET/CT up to 2 weeks prior to first dose of therapy, after completion of the first treatment course (day 21), and after completion of the fourth treatment course (day 84).

Official Title
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FDG-PET/CT as a Biomarker for Treatment Response in Advanced Melanoma

Conditions
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Recurrent Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma

Intervention / Treatment
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* Diagnostic Test: [18F]fluorodeoxyglucose
* Other: Molecular assays on biopsied tissue
* Device: positron emission tomography
* Device: computed tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have signed Institutional Review Board (IRB)-approved informed consent documentation Subjects must be diagnosed with histologically proven stage IV (metastatic) melanoma or stage III with bulky disease which may or may not be amenable for surgery and are receiving therapy at present Subjects must be scheduled to begin treatment through the Vanderbilt-Ingram Cancer Center (VICC) Melanoma Program; this will include patients receiving standard-of-care chemotherapy, targeted therapy, and/or immunotherapy, as well as patients accrued to VICC clinical trials for the study of investigational agents Subjects must have measurable disease by CT or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; to comply with PET Response Criteria in Solid Tumors (PERCIST) criteria, subjects should have at least one lesion measuring at least 2 cm in the longest diameter Exclusion Criteria: Subjects who are pregnant or nursing; urine pregnancy test/or serum human chorionic gonadotropin (HCG) will be performed on women of child bearing potential Subjects who have experienced allergic or other adverse reactions in response to intravenous injection of fluorinated radiotracers and other contrast media used in PET/CT Subjects incapable of giving informed written consent, for the following reasons: Inability to adhere to the experimental protocols for any reason Inability to communicate with the research team Limited ability to give informed consent due to mental disability, altered mental status, confusion, or psychiatric disorders Prisoners or other individuals deemed to be susceptible to coercion

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FDG-PET/CT<br>Patients undergo [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) up to 2 weeks prior to first dose of therapy, after completion of the first treatment course (day 21), and after completion of the fourth treatment course (day 84). Molecular assays on biopsied tissue obtained from a subset of patients will also undergo molecular assays, the results from which will be correlated with FDG-PET/CT data. | Diagnostic Test: [18F]fluorodeoxyglucose<br>* FDG is administered intravenously approximately 60 minutes prior to the start of PET image acquisition.<br>* Other names: fluorodeoxyglucose F-18;Other: Molecular assays on biopsied tissue<br>* Correlative studies<br>* Other names: tissue microarray;Device: positron emission tomography<br>* Undergo FDG-PET/CT<br>* Other names: tomography, emission computed;Device: computed tomography<br>* CT that is part of FDG-PET/CT is a low-milliampere, low-resolution scan that is used for anatomic localization and attenuation correction for PET images.<br>* Other names: tomography, computed;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in the Sum of the Longest Dimension of Target Lesions, Defined by RECIST | The primary imaging metric is percent change in average FDG standardized uptake value (SUV) among the same target lesions between baseline and images acquired after completion of cycle 1. The relationship between tumor SUV change and size change will be assessed using standard linear regression. | Baseline to the completion of 6 courses of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (OR) | The ability of the percent change in average standardized FDG uptake to predict OR will be assessed using the proportional odds model. | Day 84 | 
| Progression-free Survival (PFS) | Cox (proportional hazards) regression will be used to assess the association between the percent change in average standardized FDG uptake and PFS. | Time from first treatment until objective tumor progression or death for any reason, assessed up to 7 years | 
| Changes in Tumor [18F]Fluorodeoxyglucose (FDG) Accumulation | The association between the changes in tumor FDG accumulation with a panel of immunohistochemical biomarkers will be assessed with the Spearman correlation statistic. 95% confidence intervals will be calculated for each variable. Paired changes in biomarker expression between biopsied (i.e., baseline) and biopsy samples will be compared using the nonparametric Wilcoxon signed rank test. Change in binary expression will be compared using McNemar's test. The Wilcoxon rank sum test (or Kruskal Wallis test for more than 2 groups) will be used to compare continuous and ordinal variables. | Baseline to day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fluorodeoxyglucose, FDG, PET/CT, melanoma, imaging biomarkers, cancer imaging