This is a pilot study designed to evaluate the cutaneous effect of systemic inhibition of the tyrosine kinase pathway in the presence or absence of solar simulated light exposure. A maximum of 45 subjects will be accrued into the overall study we anticipate approximately 25 patients in the Raf inhibitor group and 10 patients each into the Tyrosine Kinase and MEK inhibitor arms of the study.
The study will evaluate the modulatory effect of systemic Raf inhibition in the MEK/ERK and PI3 /Akt/mTOR pathways in patients undergoing targeted therapy for metastatic disease. Changes in relevant proteins will be evaluated using a combined protein expression methodology that in includes immunohistochemistry (IHC) and reverse phase protein microarray (RPPA) technology. The primary endpoint of this study will be assessed in normal skin and skin acutely exposed to solar simulated light
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
45
A Multiport UV Solar Simulator Model 600 (Solar Light Co., Inc., Philadelphia, PA) will be used to administer Solar Simulated Light (SSL) exposures to formerly unexposed buttock skin.The device is equipped with six 8mm liquid light guides (LLG), allowing for 6 simultaneously conducted exposures.A large 3x2 endplate places the LLGs several centimeters apart and is specifically designed for Sun Protection Factor (SPF) and photo patch testing. The dose of emission from each LLG can be precisely regulated and the spectrum of emission can be limited to UVA (320-390 nm) or UVB+UVA (290-390 nm). The operator can select between UVA only and a combined Ultraviolet-A (UVA)/ Ultraviolet-B (UVB) spectrum by placement of an optical filter. The spectral output (indicated below) follows the distribution of sunlight from 290 to 390 nm.
University of Arizona Cancer Center
Tucson, Arizona, United States
Modulatory effect of systemic Raf inhibition in the MEK/Erk and PI3 /AKT/mTOR pathways in patients undergoing targeted therapy for metastatic disease
The primary endpoint of the study is to evaluate the modulatory effect of systemic Raf inhibition in the MEK/Erk and PI3 /AKT/mTOR pathways in patients undergoing targeted therapy for metastatic disease. Changes in relevant proteins will be evaluated using a combined protein expression methodology that in includes immunohistochemistry (IHC) and reverse phase protein microarray (RPPA) technology. The primary endpoint of this study will be assessed in normal skin and skin acutely exposed to solar simulated light.
Time frame: 2 months
Downstream modulation of direct Ras and MEK inhibition in human keratinocytes and melanocytes following acute solar simulated light exposure in the presence of metastatic disease treatment with Tyrosine kinase and MEK inhibitors.
The modulatory effect will be evaluated using IHC and RPPA technology.
Time frame: 2 months
Modulatory effect of systemic Raf inhibition in the MEK/Erk and PI3 /AKT/mTOR pathways in eligible melanocytic nevi.
Time frame: 2 months
Correlate the type and severity of cutaneous squamous cell carcinoma development in patients treated with BRaf inhibitors and the modulatory profile identified in the proposed primary endpoint.
Time frame: 2 months
Safety of performing solar simulated light studies in patients undergoing Ras inhibition for metastatic disease.
Time frame: 2 months
Modulatory effect of Ras inhibition in Epidermal Growth Factor Receptor (EGFR) and Activating Protein-1 (AP1) signaling pathways (IHC and RPPA).
Time frame: 2 months
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