Clinical trial NCT06479070: Prognostic Value of Measuring CtDNA in a Cohort of Patients With Stage III and IV Upper Aero-digestive Tract (UADT) Cancer , Treated With Curative RADiOtherapy With or Without Concomitant Treatment.
Official title: Prognostic Value of Measuring Circulating Tumor DNA in a Cohort of Patients With Stage III and IV UADT Cancer, Treated With Curative RADiOtherapy With or Without Concomitant Treatment.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: SCC - Squamous Cell Carcinoma
Upper Aero-digestive Tract (UADT) Neoplasm
Keywords: Squamous Cell Carcinoma
upper aero-digestive trac tumor
Ct DNA
Radiotherapy
Head and neck cancer
Lead sponsor: Institut de Cancérologie de Lorraine
Sponsor class: OTHER
First posted: 2024-06-27
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Cohorte, prospective and multicenter study.
Primary purpose: OTHER

Brief summary: Squamous cell carcinomas of the upper aero-digestive tract (SCC-UADT) represent the seventh cause of cancer and affect approximately 600,000 patients per year worldwide. The majority of UADT cancers are diagnosed at an advanced stage (70.3% at stage III and IV) and less than 60% of these patients are free of the disease at 3 years, despite aggressive multimodal local treatment by surgery and /or radiochemotherapy. The average progression-free survival (PFS) at 2 years varies between 45 and 60% depending on the studies. Tumor recurrence is most often incurable. To our knowledge, no study has demonstrated the benefit of early evaluation of the rate of decrease in ctDNA at 1 month after the end of radiotherapy alone or associated with concomitant treatment, as a predictive factor of PFS in UADT squamous cell carcinomas regardless of their HPV status. The main objective of this study is to evaluate the value of measuring the quantity of circulating tumor DNA (ctDNA) at 1 month post-treatment as a predictive factor for PFS at 24 months.

Detailed description: This is a prospective, multicenter cohort study carried out on a total of 188 patients suffering from non-metastatic stage III and IV SCC-UADT (oral cavity, larynx, oropharynx, hypopharynx, maxillary sinus), naïve to any treatment during a consultation or day hospitalization during the radiotherapy consultation.

The objective of the study is to evaluate the value of measuring the quantity of circulating tumor DNA (ctDNA) at 1 month post-treatment as a predictive factor for PFS at 24 months. This objective will be achieved by quantitatively measuring the number of copies of methylated ctDNA of genes of interest per mL of plasma; This measurement of ctDNA will be evaluated by the rate of decrease in ctDNA between the centering scanner sample and 1 month post-treatment. Two groups will be then considered: patients with a reduction ≥ 85% and those with a reduction \< 85%.

In addition, the interest of measuring the quantity of ctDNA at 1 month post-treatment as a predictive factor of overall survival (OS) and specific survival (SS) at 24 months, the kinetics of the evolution of the quantities of ctDNA during the treatment and during follow-up up to 24 months and the evolution of ctDNA quantities during treatment and follow-up as a predictive factor for PFS and OS at 24 months will also be evaluated during this study. . The analyzes will be carried out in subgroups of populations according to their p16 status (HPV viral protein) and according to the presence or absence of concomitant treatment (Cisplatin or Cetuximab).

Eligibility criteria: Inclusion Criteria

* OMS 0 to 2;
* Patient suffering from UADT squamous cell carcinoma, newly diagnosed and histologically proven, regardless of the p16 protein status, naïve to any treatment for this cancer;
* Non-metastatic cancer of stages III (N1), IVa (N1 minimum) or IVb;
* Cancer localized in the oral cavity, larynx, oropharynx, hypopharynx and maxillary sinus;
* Patient for whom treatment with curative radiotherapy associated or not with concomitant treatment (Cisplatin or Cetuximab) has been validated in a multidisciplinary consultation meeting (RCP);
* Patient capable and willing to follow all study procedures in accordance with the protocol;
* Patient having understood, signed and dated the consent form communicated on the day of inclusion;
* Patient affiliated to the social security system.

Exclusion Criteria:

* Minor patient;
* Cancer located in the cavum, ethmoidal sinus, salivary glands and skin (cutaneous squamous cell carcinoma);
* Patient already treated for UADT tumor;
* Patient treated with immunotherapy;
* Patient who has already had cancer within 5 years (cancer other than in the UADT sphere);
* OMS \> 2;
* Contraindication to radiotherapy treatment associated or not with concomitant treatment;
* Patient already included in another therapeutic trial;
* Metastatic disease (stage IVc);
* Pregnant woman, who may be pregnant, or currently breastfeeding;
* Persons deprived of liberty or under guardianship (including curatorship).

Primary outcomes:
measure: To evaluate the value of measuring the quantity of circulating tumor DNA (tcDNA) at 1 month post-treatment as a predictive factor for progression-free survival at 24 months.
timeFrame: At 1 month post-treatment
Secondary outcomes:
measure: Evaluate the value of measuring the quantity of ctDNA at 1 month post-treatment as a predictive factor for overall survival and specific survival at 24 months.
timeFrame: At 1 month post-treatment
measure: Study the kinetics of the evolution of ctDNA quantities during treatment and during follow-up up to 24 months.
timeFrame: During treatment and follow-up up to 24 months.
measure: Evaluate the evolution of ctDNA quantities during treatment and follow-up as a predictive factor for progression-free survival and overall survival at 24 months.
timeFrame: At 24 months.
measure: Evaluate the discriminatory capacity of ctDNA at 1 month post-treatment to predict response to treatment at 24 months.
timeFrame: At 1 month post-treatment
measure: Compare the clinico-pathological characteristics according to the 2 defined groups: patients with a ≥ 85% decrease in ctDNA between the centration scanner sample and the sample at 1 month post-treatment and those with a decrease <85%.
timeFrame: 1 month.
measure: Analyze the populations into subgroups according to their p16 status (HPV viral protein) and according to the presence or absence of concomitant treatment (Cisplatin or Cetuximab).
timeFrame: at 24 months post-treatment.
Other outcomes:
Locations:
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
state: Grand-Est
city: Besançon
country: France
facility: CHU Besançon
city: Dijon
country: France
facility: Centre Georges-François Leclerc
city: Reims
country: France
facility: Intitut Jean Godinot
city: Strasbourg
country: France
facility: Institut de Cancérologie Strasbourg Europe
Study officials:
affiliation: Institut de Cancérologie de Lorraine
name: FAIVRE JCF JEAN-CHRISTOPHE, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de Cancérologie de Lorraine
name: MARTZ NM NICOLAS, MD.
role: STUDY_DIRECTOR
References: