Prediction of Residual Disease by Circulating DNA Detection After Potentiated Radiotherapy for Locally Advanced Head and Neck Cancer

NCT05710679 | Recruiting

• 1 other identifier: 2022-A01668-35
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 3

Brief Summary

Sixty percent of newly diagnosed head and neck squamous cell carcinomas (HNSCCs) are at a locally advanced (LA) stage. Depending on tumor site, stage, and resectability, locoregional failure rates can range from 35% to 65%. The persistence of residual disease at the end of treatment is a major prognostic element but is not always reliably assessed by current imaging techniques. Up to 40-50% of patients have residual adenomegaly and only 30% have viable disease when further adenectomy is performed. Sensitive and reproducible detection of residual disease after treatment is a major challenge in this patient category. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) guided surveillance, with a negative predictive value of 95-97%, has proven to be non-inferior to cervical curage in HNSCCs with residual adenomegaly. Cervical curage is now indicated only if the response assessed by PET-CT is incomplete. Nevertheless, the ability of PET-CT to predict treatment failure is unsatisfactory due to a high frequency of false positives, because of inflammatory changes, with a positive predictive value of about 20-50%. Circulating tumor DNA (ctDNA) may provide a more reliable assessment of response to potentiated radiotherapy. Liquid biopsy monitoring of response in patients treated with potentiated radiation therapy for locally advanced HNSCCs a has been shown to be feasible. In 85% of patients, ctDNA is detectable and correlates significantly with tumor volume and response to treatment. In addition, one study showed that post-radiotherapy analysis of circulating HPV16 viral DNA (cvDNA) in patients with HPV16-related HNSCCs complemented PET-CT and helped guide management decisions. HPV16 cvDNA and PET-CT have similar negative predictive values, whereas the positive predictive value is higher for HPV16 cvDNA (100% versus 50%). Nevertheless, current data are insufficient to allow routine use of this marker. This is a multicenter, single arm, open study for patients with a locally advanced head and neck cancer for which a potentiated radiotherapy is indicated.

Conditions

Locally Advanced Head and Neck Carcinoma

Outcome Measures

Primary Outcomes (1)

• Rate of patients with incomplete cervical lymph node response on PET-CT after radiochemotherapy having circulating DNA (cDNA)

  Presence/absence of circulating DNA after treatment versus presence/absence of residual disease

  3 months after potentiated radiotherapy

Secondary Outcomes (8)

• cDNA detection rate among patients with residual adenomegaly after treatment

  at three-months after potentiated radiotherapy.

• Assessment of the prognostic value of cDNA detection 3 months after the end of radiochemotherapy for patients with residual adenomegaly

  at three-months after potentiated radiotherapy.

• Assessment of the prognosis value of the presence of residual adenomegaly

  At month 27

• Rate of concordance of mutational profiles and Human papillomavirus-high risk (HPV-HR) genotypes between the primary tumor and cDNAs at diagnosis

  Inclusion

• Rate of concordance between p16 immunohistochemistry and HPV-HR genotyping on the primary tumor

  Inclusion

Study Arms (1)

Interventional

EXPERIMENTAL

Biological: Blood sample

Interventions

Blood sample BIOLOGICAL

The intervention consist in a blood sample that will be taken twice : * at the inclusion (before treatment) * 3 months after the radiochemotherapy in case of incomplete response (PET-CT)

Interventional

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and ≤ 80 years
• Histologically confirmed, never treated squamous cell carcinoma with lymph node involvement
• squamous cell carcinoma p16+or p16-, stage III (N1), IVa or IVb (UICC classification 8th edition), N1 minimum, and oropharyngeal sqamous cell carcinomas p16+ stage I or II, N1 minimum, resectable but not operated or unresectable, with indication for concomitant or sequential radiochemotherapy with induction chemotherapy using Docetaxel, Platinum, 5-Fluorouracil (TPF or modified TPF according to the practices of the investigating centers)
• Oral cavity, oropharynx, hypopharynx or larynx, cervical adenopathies without primary
• Availability of FFPE samples prior to treatment initiation
• Detection of circulating DNA in the initial blood sample
• Obtaining informed consent from the patient
• Affiliation to the French social security system

You may not qualify if:

• Tumor of the nasopharynx, sinuses, nasal cavity, salivary glands or thyroid cancer
• Treatment by exclusive radiotherapy
• Contraindication to cervical lymph node dissection
• Metastatic disease (stage IVc)
• Previous treatment for head and neck cancer
• History of other cancer in the last 3 years (except carcinoma in situ, basal cell skin carcinoma, localized prostate cancer Gleason 6)
• Pregnant or breastfeeding woman
• Patient under guardianship or curators
• Psychological disorder (cognitive disorders, vigilance disorders, etc.) or social reasons (deprivation of liberty by judicial or administrative decision) or geographical reasons that could compromise the medical follow-up of the trial or compliance with the treatment

Sponsors & Collaborators

• Centre Jean Perrin: lead
• GIRCI Auvergne Rhône-Alpes: collaborator

Study Sites (3)

Centre Jean PERRIN

Clermont-Ferrand, Puy-de-Dôme, 63011, France

RECRUITING

Hôpital de la Croix-Rousse

Lyon, France

RECRUITING

CHU de Saint-Étienne

Saint-Etienne, France

RECRUITING

Related Publications (1)

• Ginzac A, Ferreira MC, Cayre A, Bouvet C, Biau J, Molnar I, Saroul N, Pham-Dang N, Durando X, Bernadach M. Prediction of residual disease using circulating DNA detection after potentiated radiotherapy for locally advanced head and neck cancer (NeckTAR): a study protocol for a prospective, multicentre trial. BMC Cancer. 2023 Jul 4;23(1):621. doi: 10.1186/s12885-023-11136-2.

  PMID: 37400806 BACKGROUND

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Maureen BERNADACH, MD

  Centre Jean Perrin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angeline GINZAC COUVÉ, PhD

CONTACT

0463663337; angeline.ginzac@clermont.unicancer.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Biological samples of patients included in the study (i.e., patients treated with radiochemotherapy for a locally advanced head and neck cancer) will be analysed (Next generation sequencing (NGS)): * At inclusion : a FFPE block + a blood sample to identify tumor specific variants (tcDNA and cvDNA) * 3 months after radiotherapy in case of incomplete response (PET-CT) : a blood sample to search if the tumor specific variants identified before the treatment are found Patients with incomplete response after 3 months radiochemotherapy will undergone a salvage adenectomy. The main objective is to assess the ability of circulating DNA to predict residual disease during salvage adenectomy.

Study Record Dates

• First Submitted: January 13, 2023
• First Posted: February 2, 2023
• Study Start: January 17, 2024
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): July 1, 2031
• Last Updated: August 13, 2025

Record last verified: 2025-07

Locations

FR (3)