Upper Gingival Squamous Cell Carcinoma
Conditions
Keywords
Upper aero-digestive tract tumours, FCGR3A and FCGR2A receptor polymorphism, Cetuximab efficacy
Brief summary
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.
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
Interventions
DRUGCetuximab
Blood sample for identifying the polymorphism of FCGR3A and FCGR2A genes
Sponsors
Institut Bergonié
Study design
Observational model
OTHER
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Polymorphism of FCGR2 Gene | At treatment initiation | 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. |
| Polymorphism of FCGR3A Gene | At treatment initiation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 4-month Non-progression Rate According to the Polymorphism | 4 months after treatment initiation | 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. |
| Overall Survival Rate | 12 months | 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 |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UGSCS Patients with Upper Gingival Squamous Cell Carcinoma initiating Cetuximab treatment
Cetuximab: Blood sample for identifying the polymorphism of FCGR3A and FCGR2A genes | 121 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 3 |
Baseline characteristics
| Characteristic | UGSCS | — |
|---|---|---|
| Age, Continuous | 60.9 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment France | 121 participants | — |
| Sex: Female, Male Female | 25 Participants | — |
| Sex: Female, Male Male | 96 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 87 / 121 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
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.
Time frame: At treatment initiation
Population: Population with FCGR2 gene contributive results
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGSCS | Polymorphism of FCGR2 Gene | RR | 29 Participants |
| UGSCS | Polymorphism of FCGR2 Gene | RH | 53 Participants |
| UGSCS | Polymorphism of FCGR2 Gene | HH | 36 Participants |
Primary
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.
Time frame: At treatment initiation
Population: Population with FCGR3 gene contributive results
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGSCS | Polymorphism of FCGR3A Gene | FF | 54 Participants |
| UGSCS | Polymorphism of FCGR3A Gene | FV | 48 Participants |
| UGSCS | Polymorphism of FCGR3A Gene | HH | 15 Participants |
Secondary
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.
Time frame: 4 months after treatment initiation
Population: Population with either FCGR2 gene contributive results or FCGR3 gene contributive results
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UGSCS | 4-month Non-progression Rate According to the Polymorphism | Non progression | 18 Participants |
| UGSCS | 4-month Non-progression Rate According to the Polymorphism | Progression | 23 Participants |
| UGSCS With Polymorphism Other Than FCG2RA = HH or FCG3RA = VV | 4-month Non-progression Rate According to the Polymorphism | Non progression | 47 Participants |
| UGSCS With Polymorphism Other Than FCG2RA = HH or FCG3RA = VV | 4-month Non-progression Rate According to the Polymorphism | Progression | 30 Participants |
Secondary
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
Time frame: 12 months
Population: Population with either FCGR2 gene contributive results and FCGR3 gene contributive results and follow-up data available
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UGSCS | Overall Survival Rate | 10.16 months |
| UGSCS With Polymorphism Other Than FCG2RA = HH or FCG3RA = VV | Overall Survival Rate | 10.48 months |