STAT3 DECOY in Head and Neck Cancer

Preliminary Assessment of the Safety and Biological Activity of Intratumoral STAT3 DECOY in Surgically Resectable Head and Neck Squamous Cell Carcinoma

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:

1. To assess the safety of a single dose of intratumoral STAT3 decoy.
2. To estimate the effect of STAT3 decoy therapy on STAT3 activation levels, STAT3-mediated gene expression, and apoptosis in treated tumors.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: STAT 3 DECOY

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of head and neck squamous cell carcinoma(primary or recurrent) amenable to surgical resection.
• ECOG performance status of 0, 1, or 2.
• Adequate organ function
• Age greater than or equal to 18 years
• Written informed consent.
• Patients with second primary lesions will be eligible for this trial.
• Negative pregnancy test, nonlactating, and using effective means of contraception if childbearing potential.

Exclusion Criteria:

• Subjects who fail to meet the above criteria.
• Subjects who are pregnant.
• Subjects with an ECOG performance status >2.
• Subjects with tumors that are too small to biopsy prior to resection and reserve a portion of the resected specimen for research purposes.
• Subjects who receive neoadjuvant radiotherapy and/or chemotherapy within four week prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A; STAT 3 decoy administration	Drug: STAT 3 DECOY; single administration to a head and neck tumor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate the safety of a single injection.	pre and post surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate the biological activity by observing the consequences of STAT3 decoy administration on STAT3 activation and target gene expression in the tumor.	pre and post surgery

Collaborators and Investigators

• Sponsor: University of Pittsburgh

Publications and helpful links

General Publications

• Sen M, Thomas SM, Kim S, Yeh JI, Ferris RL, Johnson JT, Duvvuri U, Lee J, Sahu N, Joyce S, Freilino ML, Shi H, Li C, Ly D, Rapireddy S, Etter JP, Li PK, Wang L, Chiosea S, Seethala RR, Gooding WE, Chen X, Kaminski N, Pandit K, Johnson DE, Grandis JR. First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy. Cancer Discov. 2012 Aug;2(8):694-705. doi: 10.1158/2159-8290.CD-12-0191. Epub 2012 Jun 20.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (ACTUAL): August 1, 2011
• Study Completion (ACTUAL): August 1, 2011

Study Registration Dates

• First Submitted: June 10, 2008
• First Submitted That Met QC Criteria: June 11, 2008
• First Posted (ESTIMATE): June 12, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): July 23, 2015
• Last Update Submitted That Met QC Criteria: July 22, 2015
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: STAT 3 DECOY
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: 07-022