Trial Information

Randomized Phase III Trial to Compare Radiation Therapy Alone With Radiation Therapy and Concomitant Anti-EGFr Antibody (C225) for Locally Advanced Squamous Cell Carcinomas of the Head and Neck

OBJECTIVES:

- Compare the rate of locoregional disease control maintained for 1 year in patients with
advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx treated with
radiotherapy with or without concurrent cetuximab.

- Compare the response rates, progression-free survival and overall survival rates, and
quality of life in patients treated with these regimens.

- Compare acute and late toxicity of these regimens in these patients.

- Determine tumor epidermal growth factor receptor levels in patients treated with these
regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by Karnofsky
performance status (60-80% vs 90-100%), nodal stage (N0 vs N+), tumor stage (T1-3 vs T4),
and radiotherapy schedule (concurrent boost vs once daily vs twice daily).

Patients are randomized to 1 of 2 treatment arms:

- Arm I: Patients undergo radiotherapy beginning on day 1. Patients are assigned to 1 of
3 radiotherapy groups:

- Group 1: Patients undergo concurrent boost radiotherapy comprised of radiotherapy
once daily 5 days a week for 3.5 weeks followed by radiotherapy twice daily 5 days
a week for 2.5 weeks.

- Group 2: Patients undergo radiotherapy once daily 5 days a week for 7 weeks.

- Group 3: Patients undergo radiotherapy twice daily 5 days a week for 6-6.5 weeks.

- Arm II: Patients receive a test dose of cetuximab IV over 10 minutes on day 1. Patients
who do not experience grade 4 anaphylactic reaction receive a loading dose of cetuximab
IV over 2 hours beginning 30 minutes after completion of test dose. Patients receive
maintenance cetuximab IV over 1 hour on day 8. Maintenance cetuximab repeats every week
for 7 courses. Beginning on day 8, patients undergo radiotherapy as in arm I
concurrently with maintenance cetuximab. There must be an hour interval between the
completion of cetuximab infusion and the start of any radiotherapy.

Patients with more than N1 neck disease at initial presentation undergo neck dissection 4-8
weeks after the completion of radiotherapy.

Quality of life is assessed before initiation of study therapy, at 8 weeks, and then every 4
months for 1 year.

Patients are followed at 8 weeks, every 4 months for 2 years, and then every 6 months for 3
years.

PROJECTED ACCRUAL: Approximately 416 patients (208 per arm) will be accrued for this study
within approximately 5 years.