Trial Information

Neoadjuvant Cetuximab Monotherapy Followed by Surgery in Squamous Cell Carcinoma of Head and Neck: Phase I/II Study

This is a Phase I/II trial of neoadjuvant cetuximab monotherapy in the preoperative
treatment of patients with operable HNSCC. It is a monocenter study (St-Luc university
Hospital, Université catholique de Louvain, Brussels).

This part of the trial will determine the safe minimum delay between the neoadjuvant
cetuximab infusion and surgery. The aim is to investigate if cetuximab given 24 hours before
surgery is safe.

Patients will receive cetuximab with a loading dose of 400 mg/m2 for the first
administration followed by 250 mg/m2/week at the second and third administrations, if
applicable. The delay between the last administration of cetuximab and surgery will be
progressively reduced (Figure 1).

Five levels are pre-defined before final administration of 3 preoperative doses of cetuximab
with a 24-hour delay between the last dose of cetuximab and surgery.

Level I: 10-12 days delay between the second cetuximab infusion and surgery (total of 2
doses pre-op) Level II: 6-8 days delay between the second cetuximab infusion and surgery
(total of 2 doses pre-op) Level III: 3-4 days delay between the second cetuximab infusion
and surgery (total of 2 doses pre-op) Level IV: 3-4 days delay between the third cetuximab
infusion and surgery (total of 3 doses pre-op) Level V: 24-hour delay between the third
cetuximab dose and surgery (total of 3 doses pre-op) The cohort size is 3 patients per
level, extended to 6 patients if one "limiting toxicity" is observed. Decision rules are the
same than as in any classic 3+3 phase 1design (Figure 2).

"Limiting toxicity" is defined as (i) any life-threatening (grade 4) surgical complication
or (ii) an unexpected surgical grade 3 toxicity. Unexpected toxicity will be determined by
the safety committee after careful review of the patient file.

The safety committee will consist of the surgical team of UCL Saint-Luc, one external
surgeon, one representative from Merck and the study coordinators.

Patients treated at level V will be evaluated like patients in the phase II part.