GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer
This phase II trial studies how trametinib effects tumor cells in patients with oral cavity squamous cell carcinoma that can be removed by surgery. Trametinib may shrink the tumor by blocking an enzyme pathway needed for cell growth.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Window of Opportunity Trial With GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer|
- To analyze tumor specific changes in putative tumor initiating cell populations as defined by cell surface CD44 and intracellular phospho-ERK1/2 staining after treatment with GSK1120212. [ Time Frame: Baseline and Day 15 ] [ Designated as safety issue: No ]
- Tumor specific findings will be analyzed for pathologic changes including proliferation (Ki-67 staining), tumor vasculature staining (microvessel density), ERK1/2 mediated changes in p27 (Kip1) & flow cytometric analysis of the peripheral blood & tumor. [ Time Frame: Baseline and Day 15 ] [ Designated as safety issue: No ]
- To measure the size of the tumors by clinical exam to define whether GSK1120212 induces a clinical response [ Time Frame: Baseline and Day 15 ] [ Designated as safety issue: No ]
- Flow cytometric analysis of the peripheral blood and tumor. [ Time Frame: Baseline, Day 14, and Day 15 ] [ Designated as safety issue: No ]
Peripheral blood - baseline and Day 14
Tumor - baseline and Day 15
- Determine whether GSK1120212 induces intratumoral metabolic changes in OCSCC using FDG-PET/CT imaging. [ Time Frame: Baseline and Day 14 ] [ Designated as safety issue: No ]
- Safety of GSK1120212 [ Time Frame: 1st 4-6 week follow-up visit ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||October 2015|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
GSK1120212 2 mg PO daily for a total of 14 days with the intent of the last pill being the day before surgery.
Trametinib (GSK1120212) is a selective MEK1 and MEK2 inhibitor with selective activity towards BRAF and RAS mutant cancer cell lines and hematopoietic cancer cells from AML and CML origins.
The rationale for this study in oral cavity squamous cell carcinomas rests on pre-clinical findings demonstrating that (a) activation of the ERK1/2 kinases is associated with aggressive features, (b) this aggressive phenotype is directly linked to expression of CD44, a cell surface hyaluronan receptor and (c) this association between activated ERK1/2 and CD44 is also identified in human cell lines and primary tumors. These data suggest that ERK1/2 is targetable biochemical pathway in CD44 expressing cells. These cells represent putative cancer stem cells or tumor initiating cells that have been associated with worse patient outcomes. Thus, the application of GSK1120212 to target OCSCC is a specific translational application of our laboratory findings.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01553851
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Ravindra Uppaluri, M.D. Ph.D.||Washington University School of Medicine|