Role of FCγRIIIA and FCγRIIA Receptor Polymorphisms (FCR-VADS)

Role of FCγRIIIA and FCγRIIA Receptor Polymorphisms in Cetuximab Activity Used in Palliative Treatment of Upper Aerodigestive Tract Tumours

Hypothesis:

Cetuximab, an anti-EGFR antibody, is used with radiotherapy in the treatment of locally advanced and inoperable upper aerodigestive tract cancers. Actually, no predictive biomarkers of Cetuximab antitumor activity are known in this setting. It has been shown recently that FCγRIIIA and FCγRIIA receptor polymorphisms played a role in antitumor activity of trastuzumab and cetuximab.

The investigators therefore hypothesized that FCγRIIIA and FCγRIIA receptor polymorphisms may play a predictive role in Cetuximab effectiveness in upper aerodigestive tract cancers with recurrence or metastatic disease that make them inaccessible to loco regional treatment.

Study Overview

• Status: Completed
• Conditions: Upper Gingival Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Cetuximab

Detailed Description

Hypothesis:

Cetuximab, an anti-EGFR antibody, is used with radiotherapy in the treatment of locally advanced and inoperable upper aerodigestive tract cancers. Actually, no predictive biomarkers of Cetuximab antitumor activity are known in this setting. It has been shown recently that FCγRIIIA and FCγRIIA receptor polymorphisms played a role in antitumor activity of trastuzumab and cetuximab.

We therefore hypothesized that FCγRIIIA and FCγRIIA receptor polymorphisms may play a predictive role in Cetuximab effectiveness in upper aerodigestive tract cancers with recurrence or metastatic disease that make them inaccessible to loco regional treatment.

This study is a multicentre prospective pharmacogenetic observational study, conducted on locally advanced and inoperable upper aerodigestive tract cancers.

• Blood sample for polymorphism identification (5 ml plastic tube with EDTA, taken at the start of treatment, at the same time as the blood samples routinely taken as part of standard care)
• Collection of medical data at inclusion and at 4 months

• Study Type: Observational
• Enrollment (Actual): 121

Contacts and Locations

Study Locations

• France
  • Aquitaine
    • Bordeaux, Aquitaine, France, 33000
      • Institut Bergonie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Squamous cell carcinomas of the upper aero-digestive tract recurrent or metastatic.

Description

Inclusion Criteria:

• Patient with recurrent or metastatic squamous cell carcinomas of the upper aero-digestive tract
• Patient with loco-regional extension not readily treatable
• 18 years
• Follow up in participant center
• Patient information and consent for study participation
• Patient presented in multidisciplinary meeting (RCP) in Aquitaine and for whom a treatment containing cetuximab has been proposed
• Belong to a social security system

Exclusion Criteria:

• Pregnancy
• Patient with psychological, social, family or geographical reason, who could not be treated or monitored regularly by study criteria,
• Patients deprived of liberty or under guardianship or who could not give consent for study participation
• Inclusion in another study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
UGSCS; Patients with Upper Gingival Squamous Cell Carcinoma initiating Cetuximab treatment	Drug: Cetuximab; Blood sample for identifying the polymorphism of FCGR3A and FCGR2A genes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polymorphism of FCGR2 Gene	Polymorphism of FCGR2A gene is expressed according to 3 modalities : RR / RH / HH Genomic DNA will be extracted from whole blood tubes and redissolved in 100 µl 1× TE buffer and purified on GFX columns (Amersham-Biosciences). The quantity and quality of the DNA will be checked by agarose gel electrophoresis in the presence of ethidium bromide. Polymorphisms will be detected by PCR followed by pyrosequencing.	At treatment initiation
Polymorphism of FCGR3A Gene	Polymorphism of FCGR3A gene is expressed according to 3 modalities : FF / FV / VV. Genomic DNA will be extracted from whole blood tubes and redissolved in 100 µl 1× TE buffer and purified on GFX columns (Amersham-Biosciences). The quantity and quality of the DNA will be checked by agarose gel electrophoresis in the presence of ethidium bromide. Polymorphisms will be detected by PCR followed by pyrosequencing.	At treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
4-month Non-progression Rate According to the Polymorphism	The primary endpoint is the 4-month non-progression rate assessed according to RECIST criteria (or according to a clinical assessment if the patient does not undergo radiological examination). The response will be considered "no progression" in the following cases: complete response, partial response, or stable disease. In other cases (disease progression or unevaluable), the disease will be considered to be progressing. Response will be assessed at enrollment and at 4 months or until the first of the following events: disease progression or patient death.	4 months after treatment initiation
Overall Survival Rate	Overall survival: defined as the time between the first cycle of chemotherapy and the date of death, all causes. In the absence of death confirmation, survival data are censored from the date of last news	12 months

Collaborators and Investigators

• Sponsor: Institut Bergonié
• Investigators: Principal Investigator: ROBERT Jacques, PU-PH, Institut Bergonie

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2009
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: November 5, 2012
• First Submitted That Met QC Criteria: April 9, 2013
• First Posted (Estimated): April 10, 2013

Study Record Updates

• Last Update Posted (Estimated): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Upper aero-digestive tract tumours; FCGR3A and FCGR2A receptor polymorphism; Cetuximab efficacy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Cetuximab
• Other Study ID Numbers: IB2009-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No