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. (CIRADOR)

December 18, 2025 updated by: Institut de Cancérologie de Lorraine

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

188

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Besançon, France, 25030
        • Recruiting
        • CHU Besançon
        • Contact:
        • Sub-Investigator:
          • BOUSTANI JB JIHANE, MD.
      • Dijon, France, 21000
        • Recruiting
        • Centre georges-François Leclerc
        • Contact:
          • TIAGO ST Sandrine
          • Phone Number: 03 80 73 75 00
          • Email: stiago@cgfl.fr
        • Sub-Investigator:
          • TRUC GT GILLES, MD.
      • Reims, France, 51100
      • Strasbourg, France, 67033
        • Recruiting
        • Institut de cancerologie Strasbourg Europe
        • Contact:
        • Sub-Investigator:
          • BRAHIMI YB Youssef, MD.
    • Caen
      • Caen, Caen, France, 14076
        • Recruiting
        • Centre Francois Baclesse
        • Contact:
    • Grand Est
      • Vandœuvre-lès-Nancy, Grand Est, France, 54500
        • Recruiting
        • Institut de Cancerologie de Lorraine
        • Contact:
        • Principal Investigator:
          • MARTZ NM Nicolas, MD.
  • Switzerland
    • Canton of Zurich
      • Zurich, Canton of Zurich, Switzerland, 8091
        • Recruiting
        • University Hospital Zurich (USZ)
        • Contact:
        • Contact:
        • Principal Investigator:
          • BALERMPAS BP Pangiolis, MD.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Interventional arm
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
Other: Blood samples

A blood sample of 20 mL (2 tubes of 10 mL) for research purposes will be collected during:

  • The day of the centering scan (Visit 1);
  • During treatment at Week 2 and Week 6 (+/- 1 week) (Visit 2 and 3);
  • The day of the post-therapeutic visit scheduled between 3 and 5 weeks after the end of radiotherapy, whether or not associated with concomitant treatment (Visit 4);
  • At each monitoring visit following radiotherapy associated or not with concomitant treatment (every 3 months for 24 months (V5 to V12 ; V12 = final visit)
  • When the disease progresses before initiation of the 2nd line of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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.
At 1 month post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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.
At 1 month post-treatment
Study the kinetics of the evolution of ctDNA quantities during treatment and during follow-up up to 24 months.
Time Frame: 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.
During treatment and follow-up up to 24 months.
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.
Time Frame: 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.
At 24 months.
Evaluate the discriminatory capacity of ctDNA at 1 month post-treatment to predict response to treatment at 24 months.
Time Frame: 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.
At 1 month post-treatment
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%.
Time Frame: 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.
1 month.
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).
Time Frame: 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.
at 24 months post-treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut de Cancérologie de Lorraine

Investigators

  • Principal Investigator: MARTZ NM Nicolas, MD., Institut de Cancerologie de Lorraine
  • Study Director: FAIVRE JCF Jean-Christophe, MD., Institut de Cancerologie de Lorraine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2024

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2029

Study Registration Dates

First Submitted

June 24, 2024

First Submitted That Met QC Criteria

June 24, 2024

First Posted (Actual)

June 27, 2024

Study Record Updates

Last Update Posted (Actual)

December 24, 2025

Last Update Submitted That Met QC Criteria

December 18, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-A00860-47

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The investigator centers responded to a feasibility questionnaire. After their agreement, they have access to the protocol, the synopsis and all the study documents as well as the eCRF for data entry.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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