Phase II Evaluation of Cetuximab (C225) Combined With Induction Paclitaxel and Carboplatin Followed by C225, Paclitaxel, Carboplatin, and Radiation for Stage III/IV Operable Squamous Cancer of the Head and Neck
- Determine the effect of induction therapy comprising cetuximab, paclitaxel, and
carboplatin followed by chemoradiotherapy comprising cetuximab, paclitaxel,
carboplatin, and radiotherapy and maintenance therapy comprising cetuximab on 1-year
event-free survival (freedom from surgery at the primary site and freedom from
recurrence and death) in patients with stage III or IV operable squamous cell cancer of
the head and neck.
- Determine the pathologic antitumor response at the primary site in patients treated
with this regimen.
- Determine disease-free and overall survival of patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Determine local/regional and distant failure rates in patients treated with this
- Determine the effect of this treatment regimen on selective biologic pathways, total
and phosphorylated epidermal growth factor receptor, ERK/MAPK, and P13K/AKT in these
OUTLINE: This is a multicenter study.
- Induction therapy (weeks 1-6): Patients receive cetuximab IV over 1-2 hours, paclitaxel
IV over 1 hour, and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36.
During week 7 or 8, patients undergo biopsy and evaluation of the primary site. Patients
then proceed to chemoradiotherapy.
- Chemoradiotherapy (weeks 9-13): Patients receive cetuximab IV over 1 hour, paclitaxel
IV over 1 hour, and carboplatin IV over 15 minutes on days 57, 64, 71, 78, and 85.
Patients also undergo radiotherapy once daily, 5 days a week, on weeks 9-13.
Patients with a positive biopsy at week 7 or 8 or persistent tumor at the primary site after
induction therapy undergo a second biopsy after chemoradiotherapy at week 14. Patients with
a negative biopsy at week 7 or 8 who achieve a complete clinical and pathological response
at the primary site OR patients whose biopsy becomes negative at week 14 receive an
additional 3-weeks of chemoradiotherapy beginning at week 15. Patients receive cetuximab,
carboplatin, and paclitaxel as in chemoradiotherapy (as outlined above) on days 99, 106, and
113. Patients also undergo radiotherapy once daily, 5 days a week, for 3 weeks (weeks
15-17). Patients with N1-N3 disease undergo neck dissection in weeks 20-21.
Patients with a positive biopsy at week 14 do not receive additional chemoradiotherapy, but
rather undergo surgical resection of the primary site in weeks 18-19. Patients with N1-N3
disease also undergo neck dissection at this time.
- Maintenance therapy: Beginning after completion of surgery and/or chemoradiotherapy,
patients receive cetuximab IV over 1 hour once weekly for 6 months in the absence of
disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
ACTUAL ACCRUAL: A total of 74 patients were accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Event-free Survival Rate at 1 Year
Event-free survival rate at 1 year was defined as the proportion of patients who did not have disease progression, primary site surgery, or death after being followed for 1 year.
Assessed at 1 year.
Harold J. Wanebo, MD
Roger Williams Medical Center
United States: Federal Government