STAT3 DECOY in Head and Neck Cancer
The primary goal of this study is to evaluate the safety of a transcription factor decoy targeting Signal Transducer and Activator of Transcription 3(STAT3) in patients with head and neck cancer. The rationale for targeting STAT3 using this approach is to decrease STAT3-mediated gene regulation. The study has the following scientific objectives:
- To assess the safety of a single dose of intratumoral STAT3 decoy.
- To estimate the effect of STAT3 decoy therapy on STAT3 activation levels, STAT3-mediated gene expression, and apoptosis in treated tumors.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Preliminary Assessment of the Safety and Biological Activity of Intratumoral STAT3 DECOY in Surgically Resectable Head and Neck Squamous Cell Carcinoma|
- Evaluate the safety of a single injection. [ Time Frame: pre and post surgery ] [ Designated as safety issue: Yes ]
- Evaluate the biological activity by observing the consequences of STAT3 decoy administration on STAT3 activation and target gene expression in the tumor. [ Time Frame: pre and post surgery ] [ Designated as safety issue: No ]
|Study Start Date:||August 2008|
|Study Completion Date:||August 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
STAT 3 decoy administration
Drug: STAT 3 DECOY
single administration to a head and neck tumor
Other Name: STAT 3 DECOY
The decision to proceed with an exploratory IND study to be conducted in a phase 0 setting was based upon the expectation that the trial will involve very limited human exposure to the STAT3 decoy, and as administered, will have no therapeutic or diagnostic intent. Rather, the trial is designed to determine if intratumoral administration of the STAT3 decoy in human head and neck tumors inhibits STAT3 target gene expression. Given the cumulative evidence supporting STAT3 as a therapeutic target in cancer, and the absence of any clinical trial to date using a STAT3 inhibitor, it was felt that there would be utility in a proof of principal study to determine if the STAT3 decoy inhibits the expression of STAT3 target genes in human head and neck cancers. To support the proposed study design, the Grandis lab carried out a kinetic study in a xenograft model of SCCHN. Preliminary results demonstrated that administration of the STAT3 decoy, but not the mutant control decoy, decreased expression of STAT3 target genes (Bcl-xL and/or Cyclin D1) at time points ranging from 1 to 6 hours.
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Jennifer Grandis, MD||University of Pittsburgh|