Clinical trial NCT00714649: Neoadjuvant Cetuximab in HNSCC Combined With Curative Surgery
Official title: Neoadjuvant Cetuximab Monotherapy Followed by Surgery in Squamous Cell Carcinoma of Head and Neck: Phase I/II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Head and Neck Cancer
Keywords: Head and Neck Squamous Cell Carcinoma treated with surgery
and/or radiotherapy
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Merck Serono International SA
First posted: 2008-07-14
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary diagnose HNSCC carcinoma patients eligible for curative surgery will be proposed the addition of 2 or 3 neoadjuvant cetuximab infusions. The main objective is to reduce to a minimal delay the time elapsing between last infusion and surgery.

Iterative biomarkers will be taken at 6 time points permitting to investigate expression gen profile and protein mutation.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* More than 18 years
* Histologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx
* patients selected for a primary surgical treatment
* No distant metastases
* No active second malignancy during the last 5 years
* No prior or concurrent evidence of uncontrolled severe pathology precluding administration of surgery
* life expectancy more than 3 months
* Not pregnant or nursing; fertile patients both male or female, must use effective contraception
* Signed informed consent
* Performance Status ECOG 0-1

Exclusion Criteria:

* Nasopharynx cancer
* Past or current malignancy other than HNSCC
* performance Status ECOG above 2
* Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
* Use of any investigationals agents within 4 weeks prior ti entry
* Previous exposure to EGFR targeting therapy
* Known grade hypersensitivity to cetuximab

Primary outcomes:
measure: To investigate the safety administration of cetuximab - Phase 1: to determine the safe minimum delay between preoperative cetuximab infusion and surgery -Phase II: to investigate the safety of the minimum delay determined in the phase I part.
timeFrame: 10 weeks
Secondary outcomes:
measure: To investigate the safety of postoperative radiation therapy in combination with cetuximab
timeFrame: 10 weeks
measure: To investigate the efficacy of cetuximab monotherapy in the pre-operative setting, using FDG-PET and PET/CT scan.
timeFrame: 10 weeks
measure: To perform translational research
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St Luc-UCL
Study officials:
affiliation: Cliniques Universitaires St Luc-UCL
name: Jean-Pascal H Machiels, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: