NCT01592721

Radiation and Cetuximab Plus Intratumoral EGFR Antisense DNA in Locally Advanced Head and Neck Squamous Cell Carcinoma

Safety and Efficacy of Radiation and Cetuximab Plus Intratumoral EGFR Antisense DNA in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: The University of Texas Health Science Center at San Antonio · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The incorporation of novel targeted therapies to radiation therapy is of particular interest in head and neck cancer and may improve efficacy without significantly increasing toxicity. The investigators hypothesize that the addition of a second EGFR-targeted agent that inhibits EGFR at the intracellular level will improve the antitumor effect of standard radiation and cetuximab. The goal of this study is to evaluate the safety, efficacy, and the biologic effects in patients with locally advanced SCCHN of an antisense gene targeting the EGFR in combination with standard therapy with radiation and cetuximab.

Detailed description

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. Objectives * 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 Ki67. * To examine the transfection of the EGFR antisense gene therapy in vivo. Subject population The investigators will enroll patients with SCCHN who are suitable for intratumoral injections of EGFR antisense. Treatment plan 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 4 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.

Conditions

• Squamous Cell Carcinoma
• Head and Neck Cancer

Interventions

Type	Name	Description
BIOLOGICAL	EGFR Antisense DNA	EGFR AS will be administered by direct intratumoral injection using direct visualization, endoscopy, or imaging-guidance (ultrasound) as clinically determined. Patients will receive a total of up to 4 weekly intratumoral injections of EGFR antisense (or less if there is no identifiable tumor) starting 2 weeks prior to radiation. 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.

Timeline

• Start date: 2013-04-01
• Primary completion: 2022-02-01
• Completion: 2022-02-01
• First posted: 2012-05-07
• Last updated: 2022-09-21
• Results posted: 2022-09-21

Locations

2 sites across 1 country: United States