Safety and Efficacy of Radiation/Cetuximab Plus EGFR Antisense DNA for Head and Neck Squamous Cell Carcinoma

Phase 1

Terminated

• Conditions: Squamous Cell Carcinoma, Head And Neck; Squamous Cell Carcinoma of the Head and Neck; Carcinoma, Squamous Cell of Head and Neck
• Interventions: Biological: EGFR Antisense DNA

• Registration Number: NCT00903461
• Lead Sponsor: University of Pittsburgh

Brief Summary

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. We 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, we plan to evaluate the addition of intratumoral EGFR antisense DNA (EGFR AS) to standard radiation with concurrent cetuximab in patients.

Detailed Description

Subject population We will enroll patients with SCCHN who are suitable for intratumoral injections of EGFR antisense. Please see eligibility criteria.

Treatment plan

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 7 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,excluding weekends and holidays, 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.

Study Timeline

• Study First Submitted: 2009-05-14
• Study First Submitted QC: 2009-05-14
• Study First Posted: 2009-05-18
• Study Start: 2012-04
• Primary Completion: 2015-03
• Study Completion: 2016-08
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-14
• Last Update Posted: 2017-02-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EGFR Antisense DNA	EGFR Antisense DNA	EGFR AS will be administered by direct intratumoral injection using direct visualization, endoscopy, or imaging-guidance (ultrasound) as clinically determined. Subjects 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. Patients will receive a total EGFR AS dose of 1.92 milligrams in 1.78 milliliters on each weekly treatment. This dose may be delivered equally in the same tumor site per weekly session, the primary tumor or cervical lymph nodes.

Primary Outcome Measures

Name	Time	Method
Disease progression	baseline, 4, 7, 10, and 13 months after study treatment.	Change in tumor size based on CT or MRI scans of the same tumor(s) of the head and/or neck as compared to baseline measurement.

Secondary Outcome Measures

Name	Time	Method
Number of adverse events associated with study treatment	2 weeks
Examine the transfection of the EGFR antisense gene therapy in vivo.	3 Years
Response rate	baseline, 4, 7, 10, and 13 months after study treatment.	Change in tumor size based on CT or MRI scans of the same tumor(s) of the head and/or neck as compared to baseline measurement.
Determine the effect of EGFR antisense therapy on EGFR and EGFR-related biomarkers.	3 years

Trial Locations

Locations (1)

Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States