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

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.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Head and Neck Carcinoma
• Intervention / Treatment: Biological: Blood sample

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Angeline GINZAC COUVÉ, PhD; Phone Number: +33 0463663337; Email: angeline.ginzac@clermont.unicancer.fr

Study Locations

• France
  • Grenoble, France
    • Not yet recruiting
    • CHU de Grenoble Alpes
    • Principal Investigator: Christian Christian, Pr
  • Lyon, France
    • Not yet recruiting
    • Hopital de la Croix-Rousse
    • Principal Investigator: Philippe CÉRUSE, Pr
  • Saint-Étienne, France
    • Not yet recruiting
    • CHU de Saint-Etienne
    • Principal Investigator: Yann LELONGE, Dr
  • Puy-de-Dôme
    • Clermont-Ferrand, Puy-de-Dôme, France, 63011
      • Recruiting
      • Centre Jean Perrin
      • Contact: Angeline GINZAC COUVÉ; Email: angeline.ginzac@clermont.unicancer.fr
      • Principal Investigator: Maureen BERNADACH, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years and ≤ 80 years
• Histologically confirmed, never treated squamous cell carcinoma with lymph node involvement
• Stage III (N1), stage IVa (minimum N1) or IVb, resectable but not operated or unresectable, with indication for potentiated radiotherapy
• 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
• Detection of tumor-specific variants in FFPE and leukocytes
• Obtaining informed consent from the patient
• Affiliation to the French social security system

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional	Biological: Blood sample; The intervention consist in a blood sample that will be taken twice : at the inclusion (before treatment); 3 months after the potentiated radiotherapy in case of incomplete response (PET-CT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients with incomplete cervical lymph node response on PET-CT after radiation therapy potentiated having circulating DNA (cDNA)	Presence/absence of circulating DNA after treatment versus presence/absence of residual disease	3 months after potentiated radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cDNA detection rate among patients with residual adenomegaly after treatment	The detection of cDNA and response on CT-Scan will be compared	at three-months after potentiated radiotherapy.
Assessment of the prognostic value of cDNA detection 3 months after the end of potentiated radiotherapy for patients with residual adenomegaly	Evaluated by overall and progression-free survival	at three-months after potentiated radiotherapy.
Assessment of the prognosis value of the presence of residual adenomegaly	Evaluated by overall and progression-free survival	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	evaluated the mutational profiles from FFPE block and the inclusion blood sample	Inclusion
Rate of concordance between p16 immunohistochemistry and HPV-HR genotyping on the primary tumor		Inclusion
Test of the concordance between real-time polymerase chain reaction (PCR) and NGS on formalin-fixed paraffin-embedded (FFPE) for simultaneous detection and genotyping of HPV-HR at diagnosis		Inclusion
Number of patients with ctDNA and cvDNA detection at diagnosis and the clinical, paraclinical and pathological features of the cancer		Through study completion, an average of 66 months
Evaluation of interobserver reproducibility of the interpretation of SUVmax measurements of residual cervical adenomegaly.	A centralized review of the PET-CT will be done by the sponsor to evaluate the reproducibility of the interpretation of SUVmax measurements of residual cervixal adenomegaly (pathological/benign/equivocal)	3 months after potentiated radiotherapy

Collaborators and Investigators

• Sponsor: Centre Jean Perrin
• Collaborators: Groupement Inter-Régional de Recherche Clinique et d'Innovation Auvergne Rhône-Alpes
• Investigators: Principal Investigator: Maureen BERNADACH, MD, Centre Jean Perrin

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: January 13, 2023
• First Submitted That Met QC Criteria: January 24, 2023
• First Posted (Actual): February 2, 2023

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: 2022-A01668-35

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No