Identification of a Gene Expression Signature Profile for Panitumumab Sensitivity in Untreated Locally Advanced Squamous Cell Cancer of the Head and Neck (SCCHN)
This trial will attempt to identify a gene expression signature profile biomarker for
panitumumab sensitivity in locally advanced, untreated SCCHN. SCCHN expresses or over
expresses EGFR in >90% of tumors. Panitumumab is a fully human IgG2 monoclonal antibody
approved for the treatment of epidermal growth factor receptor (EGFR) expressing previously
treated metastatic colorectal cancer. It competes with endogenous ligands such as epidermal
growth factor and tumor growth factor-α and blocks stimulation of the EGFR.9 Preclinical
experiments have shown that panitumumab has both direct anti-tumor activity and can activate
a cellular immune response to SCCHN.This study provides the opportunity to better define the
population of patients that would benefit from EGFR inhibition in SCCHN.
Patients will receive single agent panitumumab in a "window of opportunity" design prior to
definitive surgical or radiation therapy. The decision to treat primarily with either
surgery or RT based therapy will be based on best medical practice by the treating physician
per NCCN guidelines at www.nccn.org.
Response to panitumumab monotherapy before surgery or radiation will be evaluated as a
continuous variable, and a median split of patients will be used to develop a signature of
drug responsiveness. An Affymetrix chip based gene signature model will then be developed by
analyzing gene expression in panitumumab sensitive versus resistant tumors. Identification
of a gene expression profile for tumor sensitivity would allow for prospective trials
treating patient populations enriched for likelihood of clinical benefit from panitumumab
therapy. It is also possible that a gene signature profile for panitumumab responsiveness
identified in SCCHN could be used as a biomarker in other epithelial cancers.
Tumor response as measured by percentage decrease in PET scan SUV level or objective
evidence of tumor response (by CT scan or direct measurement) will be the basis for
examining the activity of panitumumab by means of identifying a gene expression signature
that predicts response in this patient population. Therefore, PET scan SUV levels will be
assessed at baseline prior to any treatment. If a baseline PET/CT is obtained and a lesion
identified with SUV level ≥6, an additional pre-treatment research PET/CT will be performed
after consent (prior to dose #1 panitumumab. A second research PET/CT will also be obtained
after the first dose of panitumumab as part of this research study. If no baseline PET/CT
has been obtained, a research PET will be obtained pre-treatment, if SUV level ≥6 an
additional research PET will be obtained after the first dose of panitumumab.
All subjects will undergo imaging, biopsy and a single dose of panitumumab 9mg/kg IV. Two
to three weeks after panitumumab, imaging will be repeated and a second biopsy will be
obtained (at surgery for surgery patients) and an optional biopsy for patients receiving RT.
Subjects may receive 2 additional doses of panitumumab during their standard therapy.
Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Identify a gene expression signature profile biomarker that predicts for sensitivity/response to panitumumab in untreated locally advanced SCCHN.
Plan will be to develop an Affymetrix chip based gene signature model by analyzing gene expression in panitumumab sensitive versus resistant tumors. Identification of a gene expression profile for tumor sensitivity would allow for prospective trials treating patient populations enriched for likelihood of clinical benefit from panitumumab therapy. It is also possible that a gene signature profile for panitumumab responsiveness identified in SCCHN could be used as a biomarker in other epithelial cancers.
Neal Ready, MD, PhD
United States: Food and Drug Administration
|Duke University Medical Center||Durham, North Carolina 27710|
|University of North Carolina at Chapel Hill||Chapel Hill, North Carolina 27599|