Clinical trial NCT05710679: Prediction of Residual Disease by Circulating DNA Detection After Potentiated Radiotherapy for Locally Advanced Head and Neck Cancer
Official title: Prediction of Residual Disease by Circulating DNA Detection After Potentiated Radiotherapy for Locally Advanced Head and Neck Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Locally Advanced Head and Neck Carcinoma
Lead sponsor: Centre Jean Perrin
Sponsor class: OTHER
Collaborators: name: Groupement Inter-Régional de Recherche Clinique et d'Innovation Auvergne Rhône-Alpes
First posted: 2023-02-02
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Biological samples of patients included in the study (i.e., patients treated with potentiated radiotherapy 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 potentiated radiotherapy will undergone a salvage adenectomy.

The main objective is to assess the ability of circulating DNA to predict residual disease during salvage adenectomy.
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

* 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, IVa or IVb, N1 minimum, 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
* 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

Primary outcomes:
measure: Rate of patients with incomplete cervical lymph node response on PET-CT after radiation therapy potentiated having circulating DNA (cDNA)
timeFrame: 3 months after potentiated radiotherapy
Secondary outcomes:
measure: cDNA detection rate among patients with residual adenomegaly after treatment
timeFrame: at three-months after potentiated radiotherapy.
measure: Assessment of the prognostic value of cDNA detection 3 months after the end of potentiated radiotherapy for patients with residual adenomegaly
timeFrame: at three-months after potentiated radiotherapy.
measure: Assessment of the prognosis value of the presence of residual adenomegaly
timeFrame: At month 27
measure: Rate of concordance of mutational profiles and Human papillomavirus-high risk (HPV-HR) genotypes between the primary tumor and cDNAs at diagnosis
timeFrame: Inclusion
measure: Rate of concordance between p16 immunohistochemistry and HPV-HR genotyping on the primary tumor
timeFrame: Inclusion
measure: 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
timeFrame: Inclusion
measure: Number of patients with ctDNA and cvDNA detection at diagnosis and the clinical, paraclinical and pathological features of the cancer
timeFrame: Through study completion, an average of 66 months
measure: Evaluation of interobserver reproducibility of the interpretation of SUVmax measurements of residual cervical adenomegaly.
timeFrame: 3 months after potentiated radiotherapy
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Centre Jean PERRIN
state: Puy-de-Dôme
city: Grenoble
country: France
facility: CHU de Grenoble Alpes
city: Lyon
country: France
facility: Hôpital de la Croix-Rousse
city: Saint-Étienne
country: France
facility: CHU de Saint-Étienne
Study officials:
affiliation: Centre Jean Perrin
name: Maureen BERNADACH, MD
role: PRINCIPAL_INVESTIGATOR
References: