The purpose of this study is to test two imaging techniques, one called whole body (WB) diffusion weighted (DWI) magnetic resonance imaging (MRI) (WB-DWI MRI), and another called Fluorine-18 3'-deoxy-3'-fluorothymidine positron emission tomography (PET) (F-18-FLT PET). The goal is to see whether these imaging techniques would allow the study doctors to see changes in the size of a tumor earlier for patients with metastatic melanoma receiving Pembrolizumab (MK-3475).
There is a growing body of evidence that demonstrates that tumor proliferation, measured classically by immunohistochemical evidence of increased Ki-67 expression, can be reliably determined in vivo using radiolabeled thymidine. The development of \[18F\]-fluorothymidine (FLT) PET has been reliably identified as a marker of cellular proliferation, and has been shown to identify changes in proliferation in successfully treated patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Each patient will receive pembrolizumab 200mg administered as a 30 minute intravenous (IV) infusion every 3 weeks for an indefinite period.
FLT PET/CT is increasingly being utilized as an early PD biomarker in cancer given the close association between FLT uptake and proliferative index.
Columbia University Irving Medical Center / NewYork-Presbyterian Hospital
New York, New York, United States
Prevalence of lesion detection (sensitivity)
Sensitivity of WB-DW MRI and FLT-PET imaging in lesion detection and evaluation for metastatic melanoma.
Time frame: Baseline
Difference in lesion metrics
Lesion metrics including diameter and intensity as measured by FLT-PET and WB-DWI MRI will be compared with standard RECIST and volumetric criteria as well as Immune Response Criteria (IRC).
Time frame: Baseline, 2 years
Change in patient response (immunoscore)
Assessed by programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and programmed death-ligand 2 (PD-L2) expression, quantification of infiltrating cluster of differentiation 8 (CD8+) T cells at the invasive margin and within the center of the tumor, and assessment of cluster of differentiation 2 (CD2) expression. Formalin fixed paraffin embedded sections will be used. Cluster of differentiation 3 (CD3) and CD8 will be stained for and the immunoscore will be calculated using standard methods.
Time frame: Baseline, 2 years
Change in patient response (expression levels)
Assessed by NanoString with measurement of immune related genes. Expression levels will be compared pre-treatment and post-treatment.
Time frame: Baseline, 2 years
Change in RECIST Index
Index lesions identified on the baseline standard Response Evaluation Criteria In Solid Tumors (RECIST) image set will be evaluated for changes in FLT maximum standardized uptake value (SUVmax) and standardized uptake volume (SUVvol), and changes in antibody-drug conjugate (ADC) on DWI MRI at 6 weeks compared with baseline. These early response measures will then be compared with RECIST response measurements on conventional imaging.
Time frame: Baseline, 6 weeks
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