Safety and Efficacy of Radiation/Cetuximab Plus EGFR Antisense DNA for 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. 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 the elderly (i.e. 70 years or older) or cisplatin-ineligible patients.
Carcinoma, Squamous Cell
Biological: EGFR Antisense DNA
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Safety and Efficacy Evaluation of Radiation and Cetuximab Plus Intratumoral EGFR Antisense DNA in Elderly or Cisplatin-ineligible Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma|
- To evaluate the locoregional control in elderly or cisplatin-ineligible patients with locally advanced SCCHN treated with intratumoral EGFR antisense DNA combined with standard radiation plus cetuximab. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
- To evaluate the toxicities associated with the above treatment. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- Evaluate other efficacy parameters, including the objective response rate, distant control and overall progression-free survival, and overall survival. [ Time Frame: 10 years ] [ Designated as safety issue: No ]
- Determine the effect of EGFR antisense therapy on EGFR and EGFR-related biomarkers. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Examine the transfection of the EGFR antisense gene therapy in vivo. [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||September 2021|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: 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 1.92 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.
Biological: EGFR Antisense DNA
Subject population We will enroll elderly (i.e. 70 years or older) or cisplatin-ineligible patients with SCCHN who are suitable for intratumoral injections of EGFR antisense. Please see section 3 for detailed eligibility criteria.
Treatment plan EGFR AS will be administered by direct intratumoral injection using direct visualization, endoscopy, or imaging-guidance (ultrasound) as clinically determined (see sections 5 and 7 for detailed treatment plan and dose modifications). 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 (see schema on the next page). 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 (see section 11).
|Contact: Jennifer Grandis, MD||(412) firstname.lastname@example.org|
|Contact: Rita Johnson, RN, BSN||(412) email@example.com|
|United States, Pennsylvania|
|Hillman Cancer Center||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Rita Johnson, RN 412-647-8571 firstname.lastname@example.org|
|Principal Investigator:||Jennifer Grandis, MD||University of University of Cancer Institute|