Clinical trial NCT06692556: Study of a Strategy Integrating Adjuvant Radiation Therapy Versus Strategy Based on Monitoring in the Treatment of Carcinomas Spinocellular With High Risk of Recurrence
Official title: Randomized Comparative Multicenter Phase III Study of a Strategy Integrating Adjuvant Radiation Therapy Versus Strategy Based on Monitoring in the Treatment of Carcinomas Spinocellular With High Risk of Recurrence
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Cutaneous Squamous Cell Carcinoma (CSCC)
Keywords: Squamous cell carcinomas at high risk of recurrence
Adjuvant radiotherapy
Surveillance
Peri Nervous System Sheathing
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
First posted: 2024-11-18
Enrollment: 266
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients will be randomized (ratio 1:1) using an online platform into one of the two study arms:

* "Adjuvant radiotherapy" arm (=133),
* "Surveillance" arm (n=133)
Primary purpose: OTHER

Brief summary: The goal of this clinical trial is to evaluate a strategy integrating adjuvant radiation therapy versus strategy based on monitoring in the treatment of carcinomas spinocellular with high risk of recurrence (SCC).

The investigators will compare the disease-free survival (DFS) of patients treated with adjuvant radiation therapy versus surveillance in high risk of recurrence SCC.

The main question it aims to answer is:

Is DFS different between the "adjuvant radiotherapy" group and the "surveillance" group?

Participants will:

* be distributed in one of the two arms
* will be followed up every 4 months for 2 years, then every 6 months (clinical examination, identification of concomitant treatments, imaging, quality-of-life questionnaire)
* followed up until their death or their progression whether local, regional or metastatic

Detailed description: The use of adjuvant radiotherapy appears to provide clinical benefit, both theoretically and based on available retrospective data. This is why some patients already benefit from this complementary treatment. However, given the lack of prospective data, the use of adjuvant radiotherapy is based on heterogeneous criteria, depending on the choice of the clinician in charge of the patient or the habits of his institution.

The sponsor team therefore propose to conduct a national prospective study to compare the efficacy and safety of a strategy integrating adjuvant radiotherapy versus a strategy based on surveillance in patients with SCC at high risk of recurrence.

Considering that there is no validated standard after surgery for patients with a high risk of recurrence, it is not possible to determine a standard arm and an experimental arm. This study therefore falls within the framework of a Research Involving the Human Person of Category 2.

This protocol constitutes the first prospective evaluation of adjuvant radiotherapy, within the framework of a comparative study. This study will thus make it possible to avoid the use of this therapeutic alternative, without rigorous evaluation in a prospective framework. Its robust methodology will make it possible to determine whether adjuvant radiotherapy provides a clinical benefit to patients at high risk of recurrence. It will modify the standards of care for this patient population.

Eligibility criteria: Inclusion Criteria:

* Patients ≥ 18 years of age at the time of signing informed consent to participate;
* Patient with histologically confirmed, localized skin squamous cell carcinoma; Note bene: patients with carcinoma of the external auditory canal may be included in the study;
* Patient treated with complete excision surgery (R0), regardless of margin (inframillimetric or supramillimetric);
* High risk disease defined by: presence of a microscopic PNI without/with another risk factor (among those mentioned below) OR presence of 2-3 risk factors other than microscopic PNI; Note Bene: The risk factors selected are immunosuppression (only haematopathy with or without treatment) , a tumor diameter \>20mm, specific location (lip/ear/temple), deep invasion (thickness \>6mm or invasion beyond subcutaneous fat), low differentiation or desmoplasia;
* Patient informed and having signed consent to participate in the study;
* Patient affiliated with a health insurance plan (or beneficiary of such a plan).

Exclusion Criteria:

* Patient with in situ or mixed SCC;
* History of SCC at high risk of relapse in the same territory (head and neck, trunk or limb) in the 2 years preceding the date of randomization;
* History of SCC having received systemic treatment;
* Patient with SCC located in the endonasal, intra-oral, anogenital or vulvar mucosa;
* Patient with recurrent SCC or SCC at very high risk of relapse defined by one of the following criteria:

  * PNI with \> 2 other risk factors,
  * \> 3 risk factors,
  * bone invasion,
  * immunosuppression by immunosuppressive treatments (whatever the reason).
* Patient with SCC with a single risk factor other than PNI;
* Patient with SCC with lymph node or distant metastasis;
* Patient with a history of solid cancer undergoing chemotherapy;
* Patient with a contraindication to radiotherapy;
* Patient with a history of radiotherapy in the area of the lesion;
* Participation in another clinical trial that may interfere with the assessment of the primary endpoint;
* Patient under guardianship or curatorship or deprived of liberty;
* Pregnant or breastfeeding woman.

Primary outcomes:
measure: Disease-Free Survival (DFS)
timeFrame: Up to 54 months
Secondary outcomes:
measure: Local recurrence-free survival (lrFS)
timeFrame: Up to 54 months
measure: Metastatic recurrence-free survival (mFS)
timeFrame: Up to 54 months
measure: Overall Survival (OS)
timeFrame: Up to 54 months
measure: Tolerance/toxicity
timeFrame: Up to 54 months
measure: Quality of Life (QoL)
timeFrame: Up to 54 months
measure: Interest of radiotherapy in the subgroup of patients over 75 years old
timeFrame: Up to 54 months
measure: Interest of radiotherapy in the subgroup of patients with Perineural Neoplastic Invasion (PNI)
timeFrame: Up to 54 months
Other outcomes:
measure: Progression-free survival after local recurrence salvage therapy in the Surveillance group
timeFrame: Up to 54 months
Locations:
city: Dijon
country: France
facility: Centre Georges François Leclerc
state: Côte-d'Or
city: Romans-sur-Isère
country: France
facility: Centre Hospitalier Romans - Hopitaux Drôme Nord
state: Drôme
city: Valence
country: France
facility: Centre de Radiothérapie Marie Curie
state: Drôme
city: Valence
country: France
facility: Centre Hospitalier de Valence
state: Drôme
city: Brest
country: France
facility: Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan
state: Finistère
city: Pessac
country: France
facility: Centre Hospitalier Universitaire de Bordeaux
state: Gironde
city: Épagny-Metz-Tessy
country: France
facility: Centre Hospitalier Annecy Genevois
state: Haute-Savoie
city: Paris
country: France
facility: Hôpital Bichat Claude-Bernard
state: Ile-de-France
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes
state: Ille-et-Vilaine
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire de Grenoble-Alpes
state: Isère
city: Blois
country: France
facility: Centre Hospitalier Simone Veil de Blois
state: Loir-et-Cher
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes - Hôtel-Dieu
state: Loire-Atlantique
city: Roanne
country: France
facility: Centre hospitalier de Roanne
state: Loire
city: Saint Priest en Jarez
country: France
facility: Centre Hospitalier Universitaire de Saint-Etienne - Hôpital Nord
state: Loire
city: Reims
country: France
facility: Institut Godinot
state: Marne
city: Vandoeuvre-les-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
state: MMeurthe-et-Moselle
city: Lorient
country: France
facility: Groupe Hospitalier Bretagne Sud
state: Morbihan
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire Estaing
state: Puy-de-Dôme
city: Rouen
country: France
facility: Centre Hospitalier Universitaire Rouen - Hôpital Charles Nicolle
state: Seine-Maritime
city: Amiens
country: France
facility: Centre Hospitalier Universitaire Amiens-Picardie
state: Somme
city: Toulon
country: France
facility: Hôpital d'instruction des armées Sainte-Anne
state: Var
city: Lyon
country: France
facility: Centre Léon Bérard
Study officials:
affiliation: Centre Leon Berard
name: Mona AMINI-ADLE, Dr
role: PRINCIPAL_INVESTIGATOR
References: