Safety and Efficacy of Radiation and Cetuximab Plus Intratumoral EGFR Antisense DNA in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
The Epidermal Growth Factor Receptor (EGFR) is highly expressed in SCCHN and its
overexpression is associated with poor patient outcome. EGFR is a promising target of
anticancer therapy. The investigators have developed EGFR antisense DNA as a safe and
potentially efficacious treatment for SCCHN as shown in a previous phase I study conducted
at the University of Pittsburgh. Cetuximab (Erbitux or C225) is a chimerized EGFR monoclonal
antibody that has produced positive results in a phase III trial in SCCHN when added to
radiation therapy and was approved by the FDA for the treatment of locally advanced SCCHN.
Radiation plus cetuximab is considered a standard treatment, especially for patients who are
not good candidates for chemotherapy. In the current study, the investigators plan to
evaluate the addition of intratumoral EGFR antisense DNA (EGFR AS) to standard radiation
with concurrent cetuximab in patients.
- To evaluate the safety of the combination of intratumoral EGFS AS DNA with standard
cetuximab and radiation.
- To evaluate the locoregional progression-free survival in selected patients with
locally advanced SCCHN treated with intratumoral EGFR AS DNA combined with standard
radiation plus cetuximab.
- To evaluate other efficacy parameters, including the objective response rate, distant
control and overall progression-free survival, and overall survival.
- To determine the effect of EGFR antisense therapy on EGFR-related biomarkers. The
investigators will use reverse phase protein microarrays (RPPA) and immunohistochemical
(IHC) analysis of tissue microarrays (TMA) on baseline and post-treatment tumor tissue
to determine the expression level and modulation of a panel of EGFR and EGFR-pathway
related biomarkers, including (but not necessarily limited to) EGFR, pEGFR, Src, pMAPK,
STAT3, pSTAT3, pSTAT5, pSTAT1, pAKT, p38, p21, p27, PARP, E-cadherin, p-ErbB3, and
- To examine the transfection of the EGFR antisense gene therapy in vivo.
The investigators will enroll patients with SCCHN who are suitable for intratumoral
injections of EGFR antisense.
EGFR AS will be administered by direct intratumoral injection using direct visualization,
endoscopy, or imaging-guidance (ultrasound) as clinically determined (see protocol).
Patients will receive a total of up to 7 weekly intratumoral injections of EGFR antisense
(or less if there is no identifiable tumor) starting 2 weeks prior to radiation (study
schema in protocol). Patients will receive standard radiation 70 Gy/200 cGy/daily, 5
days/week, with concurrent cetuximab 250 mg/m2, after a loading dose of 400 mg/m2 2 weeks
prior to starting radiation.
Statistical Design and Sample Size
The study will be conducted in two-stages. In the first stage, 11 patients with stage IVA-C
or recurrent disease will be evaluated for safety. If the regimen is deemed safe, a total of
31 patients with stage III or IVA-B, previously untreated SCCHN will be enrolled in the
second stage of the study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
This is a 2-stage clinical trial. In the first stage, toxicity will be the primary endpoint. Toxicity measures will be graded according to NCI CTCAE version 4.0.
Athanassios Argiris, MD
University of Texas Health Science Center San Antonio
United States: Food and Drug Administration
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