Clinical trial NCT02119559: Circulating Tumor Cells as an Early Predictive head-and -Neck Squamous-cell Carcinoma
Official title: Assessment of Circulating Tumor Cells as an Early Predictive Marker of Response to a First Line Treatment Based on an Anti-Human Epidermal Growth Factor Receptor (HER), Cetuximab, in Patients With Inoperable Recurrent and/or Metastatic Head-and-neck Squamous-cell Carcinoma.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Metastatic Head-and-neck Squamous-cell Carcinoma
Keywords: Circulating Tumor Cells
Treatment Efficiency
Biomarker
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
First posted: 2014-04-21
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: In France, the incidence of head and neck squamous cell carcinomas (HNSCC) is 16 000 new cases/year. During these last years, many new chemotherapies and targeted therapies have been developed improving significantly the overall survival of patients notably anti-HER molecules. In inoperable recurrent and/or metastatic HNSCC, the best treatment is based on an anti-Human Epidermal Growth Factor Receptor (EGFR) antibody, targeting Human Epidermal Growth Factor Receptor 1 (HER1), the Cetuximab combined with platinum +/- 5 Fluoro Uracil (5FU): " Extreme protocol ". However, no clinical or biological criteria predictive of drug efficacy have been reported yet. Thus, the development of such a predictive factor is an urgent need in HNSCC at both the clinical and pharmacy-economic level, to propose the best personalized treatment. One idea would be to enumerate and characterize the circulating tumor cells (CTC) which could give us an early evaluation of the therapeutic efficiency. In this context, the investigators have developed an innovative technology, the EPISPOT assay (patent of the University Medical Center of Montpellier), that allows the detection \& characterization of viable CTC in the peripheral blood. The EPISPOT technology has been already evaluated in the breast and prostate cancer.Thus, the investigators would like for the first time to perform a prospective study on a cohort of patients treated following the Extreme protocol, with this technology, to assess the predictive value of CTC count. The investigators will use the CellSearch® system as the reference test.

Detailed description: This is a multi-centric prospective non randomized open labeled study performed on a cohort of patients with inoperable recurrent and/or metastatic HNSCC who will be treated, with a first line treatment based on an anti-Human Epidermal Growth Factor Receptor (HER), the Cetuximab.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 yo.
* Histologically or cytologically confirmed recurrent and/or metastatic Squamous Cell Carcinoma Head and Neck (SCCHN) (excluding nasopharyngeal carcinoma) not suitable for local therapy : surgery and/or radiotherapy ; or metastatic disease with or without primary evolving tumor.
* Target definable with Response Evaluation Tumors Criteria in Solid (RECIST) 1.1 criteria.
* WHO performance status 0,1 or 2.
* Life expectancy \> 3 month at inclusion.
* Patient eligible for first line chemotherapy based on cisplatin (100 mg/m2 as a 1-hour intravenous (IV) infusion on day 1) or carboplatin (AUC 5 mg/ml.min by 1-hour IV infusion, day 1) and an infusion of 5-FU (1000 mg/m2/day for 4 days) every 3 weeks, with cetuximab (initial dose of 400 mg/m2 \[2-hour IV infusion\] followed by subsequent weekly doses of 250 mg/m2 \[1-hour IV infusion\], ending at least 1 hour before the start of chemotherapy).
* Consent form for participation signed.

Exclusion Criteria:

* Other chemotherapy protocol not involving platinum and cetuximab.
* Other proven synchronous evolving cancer.
* Evolving infectious disease or severe other disease preventing the patient from receiving treatment.
* Patient refusal.
* Patient unable to consent.
* Pregnant or breastfeeding, or premenopausal women not taking effective contraception.
* Current Participation to other clinical trial except experimental molecules.
* Vulnerable persons protected by law.
* People under guardianship

Primary outcomes:
measure: Predictive value of the CTC on the Progression Free Survival
timeFrame: Duration study 2 years
Secondary outcomes:
measure: Prognostic value of the CTC at baseline (EPISPOT) and to compare for the first time the results with those obtained with the CellSearch system.
timeFrame: Duration study 2 years
measure: Prognostic value of the CTC at baseline (EPISPOT)
timeFrame: Duration study 2 years
measure: Predictive value of the early progression of CTC (EPISPOT) on the overall survival
timeFrame: Duration study 2 years
measure: Compare for the first time the results with those obtained with the CellSearch® system
timeFrame: Duration study 2 years
measure: Evaluate the expression of EGFR in CTCs before and after administration of cetuximab (Erbitux) with both technologies and EPISPOT CellSearch ®
timeFrame: Duration study 2 years
measure: Evaluate the impact of the presence of epithelial-mesenchymal transition (EMT) marker on the prognosis
timeFrame: Duration study 2 years
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Department of Otorhinolaryngology, CHU Gui de Chauliac
Study officials:
affiliation: CHU GUI DE CHAULIAC
name: RENAUD GARREL, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garrel R, Mazel M, Perriard F, Vinches M, Cayrefourcq L, Guigay J, Digue L, Aubry K, Alfonsi M, Delord JP, Lallemant B, Even C, Daures JP, Landais P, Cupissol D, Alix-Panabieres C. Circulating Tumor Cells as a Prognostic Factor in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: The CIRCUTEC Prospective Study. Clin Chem. 2019 Oct;65(10):1267-1275. doi: 10.1373/clinchem.2019.305904. Epub 2019 Aug 6.
citation: Le Louedec F, Alix-Panabieres C, Lafont T, Allal BC, Garrel R, Digue L, Guigay J, Cupissol D, Delord JP, Lallemant B, Alfonsi M, Aubry K, Mazel M, Becher F, Perriard F, Chatelut E, Thomas F. Cetuximab pharmacokinetic/pharmacodynamics relationships in advanced head and neck carcinoma patients. Br J Clin Pharmacol. 2019 Jun;85(6):1357-1366. doi: 10.1111/bcp.13907. Epub 2019 Apr 13.