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.
- Conditions
- SCC - Squamous Cell CarcinomaUpper Aero-digestive Tract (UADT) Neoplasm
- Interventions
- Other: Blood samples
- Registration Number
- NCT06479070
- Lead Sponsor
- Institut de Cancérologie de Lorraine
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 188
Not provided
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Interventional arm Blood samples 12 blood samples will be taken from patients suffering from non-metastatic stage III and IV SCC-UADT (oral cavity, larynx, oropharynx, hypopharynx, maxillary sinus), naïve to any treatment
- Primary Outcome Measures
Name Time Method 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. At 1 month post-treatment ctDNA will be measured quantitatively as the number of copies of methylated ctDNA of the genes of interest per mL of plasma.
The ctDNA measurement will be evaluated by the rate of decrease in ctDNA between the centering scanner sample and 1 month post-treatment. Two groups will then be considered: patients with a reduction ≥ 85% and those with a reduction \< 85%.
Progression-free survival is defined by the time elapsed between the date of end of treatment (radiotherapy associated or not with concomitant treatment) and the onset of disease progression or death from all causes.
- Secondary Outcome Measures
Name Time Method 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%. 1 month. The evolution of the quantities of ctDNA before treatment, during treatment and up to 24 months of post-treatment follow-up will be evaluated as a risk factor for progression-free survival and overall survival at 24 months.
Study the kinetics of the evolution of ctDNA quantities during treatment and during follow-up up to 24 months. During treatment and follow-up up to 24 months. Overall survival is defined by the time elapsed between the date of end of treatment and the date of death from all causes.
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. At 24 months. Specific survival is defined by the time elapsed between the date of end of treatment and the date of cancer-related death.
Evaluate the discriminatory capacity of ctDNA at 1 month post-treatment to predict response to treatment at 24 months. At 1 month post-treatment The kinetics of the evolution of the quantity of ctDNA will be studied from pre-treatment, during treatment and up to 24 months of post-treatment follow-up.
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. At 1 month post-treatment ctDNA will be measured quantitatively as the number of copies of methylated tcDNA of the genes of interest per mL of plasma.
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). at 24 months post-treatment. Evaluation of partial or complete response to treatment at the last clinical evaluation at 24 months post-treatment by clinical and radiological data.
Trial Locations
- Locations (5)
Institut de Cancérologie de Lorraine
🇫🇷Vandœuvre-lès-Nancy, Grand-Est, France
CHU Besançon
🇫🇷Besançon, France
Centre Georges-François Leclerc
🇫🇷Dijon, France
Intitut Jean Godinot
🇫🇷Reims, France
Institut de Cancérologie Strasbourg Europe
🇫🇷Strasbourg, France