Neoadjuvant Cetuximab in HNSCC Combined With Curative Surgery (CHIRON)

This study has been completed.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Merck Serono International SA
Information provided by (Responsible Party):
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier:
NCT00714649
First received: July 8, 2008
Last updated: November 13, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: cetuximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Neoadjuvant Cetuximab Monotherapy Followed by Surgery in Squamous Cell Carcinoma of Head and Neck: Phase I/II Study

Resource links provided by NLM:


Further study details as provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:

Primary Outcome Measures:
  • 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. [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To investigate the safety of postoperative radiation therapy in combination with cetuximab [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
  • To investigate the efficacy of cetuximab monotherapy in the pre-operative setting, using FDG-PET and PET/CT scan. [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
  • To perform translational research [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 34
Study Start Date: July 2008
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
I-1

This is a phase I/II trial. PhaseI: The delay between the last administration of cetuximab and surgery will be progressively reduced. Five delay schedules 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. The cohort size is 3 patients per delay schedule, extended to 6 patients if one "limiting toxicity" is observed.

Phase II: will proceed if delay schedule V is safe. The patients included in delay schedule V of the Phase I part of the study will be involved in the phase II analysis. Recruitment of a total of 12 patients (3-6 of delay schedule V in phase I plus an additional 3-9 patients).

Drug: cetuximab
Cetuximab 250mg/m²/week IV before surgery till surgery

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00714649

Locations
Belgium
Cliniques Universitaires St Luc-UCL
Bruxelles, Belgium, 1200
Sponsors and Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Merck Sharp & Dohme Corp.
Merck Serono International SA
Investigators
Principal Investigator: Jean-Pascal H Machiels, MD PhD Cliniques Universitaires St Luc-UCL
  More Information

No publications provided

Responsible Party: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT00714649     History of Changes
Other Study ID Numbers: CHIRON 2008-01
Study First Received: July 8, 2008
Last Updated: November 13, 2012
Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:
Head and Neck Squamous Cell Carcinoma treated with surgery
and/or radiotherapy

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014