Randomized Phase II Feasibility Study of Cetuximab Combined With 4 Cycles of TPF Followed by Platinum Based Chemo-radiation Strategies
- To determine the safety profile of chemoradiotherapy with carboplatin vs cisplatin in
patients with newly diagnosed, unresectable stage III or IV squamous cell carcinoma of
the head and neck.
- To select one of these chemoradiotherapy regimens to be used as an experimental arm in
a future phase III trial.
- To look for EGFR expression and downstream signaling in reacting skin samples from
patients experiencing skin toxicity and in normal skin samples from the same patients
for comparison with skin samples from patients who have not shown skin toxicity.
- To explore which factors related to EGFR predict the biological activity of cetuximab
in patients treated with these regimens.
OUTLINE: This is a multicenter study.
Patients receive induction chemotherapy comprising docetaxel IV over 1 hour and cisplatin IV
over 1 hour on day 1 and fluorouracil IV continuously over 24 hours on days 1-5. Treatment
repeats every 3 weeks for up to 4 courses in the absence of unacceptable toxicity.
Within 3 weeks after completion of induction chemotherapy or within 5 weeks from the start
of the last chemotherapy course (day 21), patients are stratified by institution and
treatment response (stable disease [SD], partial response [PR], or complete response [CR] vs
non-response [progressive disease]). Patients with progressive disease are removed from
study and patients with SD, PR, or CR are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo radiotherapy (RT) (3-dimensional conformal RT or
intensity-modulated RT) on days 1-5 weekly for up to 7 weeks. Beginning on day 1 of RT,
patients receive cisplatin IV over 1 hour once weekly for up to 7 weeks.
- Arm II: Patients undergo RT as in arm I. Beginning on day 1 of RT, patients receive
carboplatin IV over 1 hour once weekly for up to 7 weeks.
Patients in both arms receive cetuximab IV over 1-2 hours once weekly beginning on day 1 of
induction chemotherapy and continuing until the end of concurrent chemoradiotherapy.
Primary tumor tissue and skin biopsies, including fixed paraffin-embedded tissue specimens
or frozen tissue, are collected at baseline (prior to treatment) and after completion of
study treatment for correlative laboratory studies of EGFR expression and downstream
signaling. Specimens are assessed by immunohistochemistry, fluorescence in situ
hybridization, and reverse transcriptase-PCR sequencing of genes and proteins for
ErbB-related activation. In the event of skin toxicity during treatment, patients undergo at
least two additional biopsies, one in reacting skin and one in normal skin. Samples are
assessed for markers of treatment efficacy related to cetuximab.
After completion of study therapy, patients are followed at 3 months and periodically
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility of the chemoradiotherapy part of the treatment, assessed as at least 80% dose intensity of any of the radiotherapy, the platinum, and cetuximab during the chemoradiotherapy part of the treatment
Jan B. Vermorken, MD, PhD
Universitair Ziekenhuis Antwerpen
United States: Federal Government