Cutaneous Squamous Cell Carcinoma (CSCC)Phase 3SPINO-RTNCT06692556
Study of a Strategy Integrating Adjuvant Radiation Therapy Versus Strategy Based on Monitoring in the Treatment of Carcinomas Spinocellular With High Risk of Recurrence
A Phase 3 study testing Adjuvant radiotherapy in people with Cutaneous Squamous Cell Carcinoma (CSCC), run by Centre Leon Berard at 28 sites in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous Squamous Cell Carcinoma (CSCC)
- What is being tested?
- Adjuvant radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 266 participants
- Where
- 28 sitesFrance
- Study dates
- 21 Feb 2025to Jun 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- I1. Patients aged ≥ 18 years at the time of signing the informed consent form; I2. Patients with histologically confirmed localized cutaneous squamous cell carcinoma;
- Note: Patients with carcinoma of the external auditory canal may be included in the study;
- I3. Patients treated with complete surgical excision (R0), regardless of the margin (submillimeter or supramillimeter);
- I4. Disease with a high risk of recurrence defined by one of the following scenarios:
- presence of microscopic EPN without any other risk factors;
- presence of microscopic EPN with a single other risk factor;
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- presence of 2 risk factors other than microscopic EPN;
- presence of 3 risk factors other than microscopic EPN;
- Note: The risk factors considered are immunosuppression (limited to untreated hematologic disease), a tumor diameter >20 mm (longest axis, measured preferably clinically, or, failing that, histologically), a specific location (lip/ear/temple), deep invasion (tumor thickness >6 mm (Breslow) or invasion beyond the subcutaneous fat), poor differentiation, or desmoplasia;
- I5. Patient informed and having signed a consent form to participate in the study; I6. Patient enrolled in a health insurance plan (or beneficiary of such a plan).
Who cannot join
- NI1. Patients with in situ or mixed CEC; NI2. History of CEC with a high risk of recurrence in the same lymphatic drainage area (head and neck, trunk, or limb) within 2 years prior to the randomization date; NI3. History of CEC treated with systemic therapy; NI4. Patients with SCC localized to the endonasal, intraoral, anogenital, or vulvar mucosa;
- NI5. Patients with recurrent SCC or SCC at very high risk of recurrence defined by one of the following criteria:
- EPN with ≥ 2 other risk factors,
- > 3 risk factors,
- bone invasion,
- immunosuppression due to immunosuppressive treatments (regardless of the reason). NI6. Patients with CEC presenting a single risk factor other than EPN; NI7. Patient with CEC and lymph node or distant metastasis; NI8. Patient with a history of cancer undergoing systemic and/or locoregional anticancer treatment;
- Note: Local treatment of cutaneous keratoses with fluoropyrimidines is permitted outside the theoretical radiation field);
- NI9. Patient with a contraindication to radiation therapy; NI10. Patient with a history of radiation therapy to the site of the lesion; NI11. Participation in another clinical trial that may interfere with the assessment of the primary endpoint; NI12. Patient under legal guardianship or conservatorship, or deprived of liberty; NI13. Pregnant or breastfeeding woman.
Trial locations and contacts
28 sites in 1 country. Contact the study team or a site near you to ask about taking part.
28 sites in 1 country
France28 sites, 20 recruiting
- Active, not recruiting
Centre Hospitalier Universitaire Amiens-Picardie
Amiens, Somme, 80054
- Recruiting
Centre Hospitalier Simone Veil de Blois
Blois, Loir-et-Cher, 41016
Guido BENS, Dr, bensgui@ch-blois.fr
Guido BENS, Dr
- Not yet recruiting
CHU de Bordeaux - Hôpital Saint André
Bordeaux, New Aquitaine, 33076
Emilie GERARD, Dr, 05 56 79 47 05 ext. 05 56 79 49 75, emilie.gerard@chu-bordeaux.fr
Marie BEYLOT-BARRY, Dr, 05 57 82 25 00, marie.beylot-barry@chu-bordeaux.fr
- Withdrawn
Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan
Brest, Finistère, 29200
- Not yet recruiting
Hôpital de la Cavale Blanche
Brest, Finistère, 29200
Gurvan DISSAUX, Dr, 02 98 22 33 98, gurvan.dissaux@chu-brest.fr
- Recruiting
Centre Hospitalier Universitaire Estaing
Clermont-Ferrand, Puy-de-Dôme, 63033
Sandrine MANSARD, Dr, +33 4 73 75 05 50, smansard@chu-clermontferrand.fr
Sandrine MANSARD, Dr
- Active, not recruiting
Centre Georges François Leclerc
Dijon, Bourgogne-Franche-Comté, 21079
- Not yet recruiting
Centre Hospitalier Universitaire de Grenoble-Alpes
La Tronche, Isère, 38700
Sabiha TRABELSI-MESSAI, Dr, +33 4 76 76 66 16, strabelsimessai@chu-grenoble.fr
Sabiha TRABELSI-MESSAI, Dr
- Not yet recruiting
Centre De Radiothérapie Guillaume Le Conquérant
Le Havre, Normandy, 76600
Paul LESUEUR, Dr, 02 35 13 66 13, p.lesueur@cglc.fr
Romain MALLET, Dr, 02 35 13 66 13, r.mallet@cglc.fr
- Withdrawn
Centre Hospitalier Emile Roux
Le Puy-en-Velay, Auvergne-Rhône-Alpes, 43000
- Recruiting
Groupe Hospitalier Bretagne Sud
Lorient, Morbihan, 56322
Caroline JACOBZONE-LEVEQUE, Dr, +33 6 16 98 31 79, c.jacobzoneleveque@ghbs.bzh
Caroline JACOBZONE-LEVEQUE, Dr
- Recruiting
Centre Léon Bérard
Lyon, 69373
Mona AMINI-ADLE, Dr, +33 4 78 78 59 96, mona.amini-adle@lyon.unicancer.fr
Mona AMINI-ADLE, Dr
- Recruiting
Centre Hospitalier Annecy Genevois
Metz-Tessy, Haute-Savoie, 74374
Julie DE QUATREBARBES, Dr, +33 4 50 63 68 63, jdequatrebarbes@ch-annecygenevois.fr
Julie DE QUATREBARBES, Dr
- Recruiting
Centre Hospitalier Universitaire de Nantes - Hôtel-Dieu
Nantes, Loire-Atlantique, 44093
Gaëlle QUEREUX, Dr, +33 2 40 08 31 44, gaelle.quereux@chu-nantes.fr
Gaëlle QUEREUX, Dr
- Not yet recruiting
Centre Antoine Lacassagne
Nice, Provence-Alpes-Côte d'Azur Region, 06189
Damien GIACCHERO, Dr, 04 93 86 73 68, Damien.giacchero@gmail.com
Dorian CULIE, Dr, 04 92 03 17 89, Dorian.culie@nice.unicancer.fr
- Active, not recruiting
Hôpital Bichat Claude-Bernard
Paris, Île-de-France Region, 75877
- Active, not recruiting
Centre Hospitalier Universitaire de Bordeaux
Pessac, Gironde, 33604
- Not yet recruiting
Hospices Civils de Lyon - Centre Hospitalier Lyon Sud
Pierre-Bénite, Auvergne-Rhône-Alpes, 69495
Emmanuel MESNY, Dr, emmanuel.mesny@chu-lyon.fr
Nicolas POULALHON, Dr, 04 78 86 45 69 ext. 04 78 86 13 29, nicolas.poulalhon@chu-lyon.fr
- Active, not recruiting
Institut Godinot
Reims, Marne, 51726
- Not yet recruiting
Centre Hospitalier Universitaire de Rennes
Rennes, Ille-et-Vilaine, 35033
Monica DINULESCU, Dr, monica.dinulescu@chu-rennes.fr
Monica DINULESCU, Dr
- Recruiting
Centre hospitalier de Roanne
Roanne, Pays de la Loire Region, 42300
Amel BLANCHARD, Dr, +33 4 77 44 32 77, amel.blanchard@ch-roanne.fr
Amel BLANCHARD, Dr
- Recruiting
Centre Hospitalier Romans - Hopitaux Drôme Nord
Romans-sur-Isère, Drôme, 26102
François SKOWRON, Dr, +33 4 75 05 75 80, f.skowron@hopitaux-drome-nord.fr
François SKOWRON, Dr
- Not yet recruiting
Centre Hospitalier Universitaire Rouen - Hôpital Charles Nicolle
Rouen, Seine-Maritime, 76031
Anne-Bénédicte DUVAL-MODESTE, Dr, +33 2 32 88 81 41, anne-benedicte.duval-modeste@chu-rouen.fr
Anne-Bénédicte DUVAL-MODESTE, Dr
- Recruiting
Centre Hospitalier Universitaire de Saint-Etienne - Hôpital Nord
Saint Priest En Jarez, Pays de la Loire Region, 42271
Elodie GUILLAUME, Dr, +33 4 77 91 71 02, elodie.guillaume@chu-st-etienne.fr
Elodie GUILLAUME, Dr
- Withdrawn
Hôpital d'instruction des armées Sainte-Anne
Toulon, Var, 83800
- Not yet recruiting
Centre de Radiothérapie Marie Curie
Valence, Drôme, 26000
Jean-Baptiste GUY, Dr, dr.guy@cmc-valence.org
Jean-Baptiste GUY, Dr
- Recruiting
Centre Hospitalier de Valence
Valence, Drôme, 26000
Florent GRANGE, Dr, +33 4 75 75 75 49, fgrange@valence.fr
Florent GRANGE, Dr
- Recruiting
Institut de Cancérologie de Lorraine
Vandœuvre-lès-Nancy, MMeurthe-et-Moselle, 54519
Sophie RENARD, Dr, +33 3 83 59 86 10, s.renard@nancy.unicancer.fr
Sophie RENARD, Dr
About this study
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
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.
Read more
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
Read the 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.
- Conditions
- Cutaneous Squamous Cell Carcinoma (CSCC)
- Being tested
- Adjuvant radiotherapy
- Keywords
- Squamous cell carcinomas at high risk of recurrence, Adjuvant radiotherapy, Surveillance, Peri Nervous System Sheathing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adjuvant radiotherapyRadiation
Patients will receive an adjuvant radiotherapy corresponding to an equivalent dose of 45 to 50 Gy (Equivalent Dose in 2 Gy Fractions [EQD2] with a tumor alpha/beta ratio of 10 Gy) delivered on the operating bed.
Patients will be treated by :
- either external radiation therapy using high-energy electrons or photons:
- 45 Gy in 15 fractions of 3 Gy
- 50 Gy in 25 fractions of 2 Gy
- or interstitial brachytherapy or brachytherapy via skin applicators:
- 36 Gy in 8 fractions of 4.5 Gy
- 36 Gy in 9 fractions of 4 Gy
- 40 Gy in 8 fractions of 5 Gy
Radiation therapy should be started within 8 weeks after surgery (or 10 if delayed healing).
Patients will be monitored regularly until the date of the first relapse (local, regional or metastatic), or until the date of death (if no relapse).
Regardless of the type of relapse, remedial treatments will be left to the the investigator's discretion up to the first metastatic relapse.
| Study group | Role | What they receive |
|---|---|---|
| Adjuvant radiotherapy | Active comparator | Radiation therapy should be started within 8 to 12 weeks after surgery.
An equivalent dose of 45 to 50 Gy will be delivered on the operating bed. The irradiation techniques used may be either external radiation therapy with high-energy photons or electrons or brachytherapy. Patients will be monitored regularly until the date of the first local, regional or metastatic relapse, or until the date of death if they do not relapse.
Regardless of the type of relapse, remedial treatments will be left to the The investigator's discretion; they will be collected in the data collection book as well as data on subsequent relapses, up to the first metastatic relapse. Receives: Radiation: Adjuvant radiotherapy |
| Surveillance | No intervention | Patients will not receive any treatment after surgery and will be monitored regularly until the date of their first local, regional or metastatic relapse, or until the date of death if they do not relapse. Regardless of the type of relapse, the treatment to be used is left to the discretion of the investigator; it will be collected in the data collection book as well as data on subsequent relapses up to the first metastatic relapse. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-Free Survival (DFS)
DFS is defined as the time from the date of randomization to the date of recurrence (local, lymph node or metastatic) or death from any cause. A new skin lesion will not be considered a statistical event. Patients without an event at the date of analysis will be censored at the last date of new disease-free status.
DFS will be estimated by the Kaplan Meier method and described in terms of median in each arm. DFS distributions will be compared between arms using a Log-Rank test. The hazard ratio from a Cox model will be calculated and presented with its 95% confidence interval. The rate of patients without recurrence at 1 and 2 years post-randomization will also be presented with their associated confidence interval.
Measured: Inclusion, every 4 months for 2 years and then every 6 months until death or progression, assessed up to 36 months of follow-up from the last patient enrolled or until the 120th event occurs (wichever comes first)
Secondary outcomes (8)
Local recurrence-free survival (lrFS)
lrFS is defined as the time from randomization (or surgery) to the first occurrence of regional recurrence or death from any cause.
Measured: Inclusion, every 4 months for 2 years and then every 6 months until death or progression, assessed up to 36 months of follow-up from the last patient enrolled or until the 120th event occurs (wichever comes first)
Regional Recurrence-Free Survival (RrFS)
RrFS is The time from randomization (or surgery) to the first occurrence of regional recurrence or death from any cause, whichever came first
Measured: Inclusion, every 4 months for 2 years and then every 6 months until death or progression, assessed up to 36 months of follow-up from the last patient enrolled or until the 120th event occurs (wichever comes first)
Metastatic recurrence-free survival (MrFS)
MrFS is defined as the time elapsed between the date of randomization and the date of metastatic recurrence or death from any cause. Patients without an event at the analysis date will be censored at the last date of news without metastatic disease.
Measured: Inclusion, every 4 months for 2 years and then every 6 months until death or progression, assessed up to 36 months of follow-up from the last patient enrolled or until the 120th event occurs (wichever comes first)
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death from any cause. Patients without an event at the analysis date will be censored at the last date of death-free news.
Measured: every 4 months for 2 years, then every 6 months until the condition progresses or the patient dies. If progression, updates annually. Assessed up to 36 months of follow-up from the last patient enrolled or until the 120th event occurs (wichever comes fir
Tolerance/toxicity
The safety will be described according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC AE) Version 5 grid by reporting the number and percentage of patients with toxicity by grade. Adverse events will be coded according to the MedDRA® dictionary and will be described by System Organ Class and Preferred Term. The number of patients with at least one AE by grade, at least one AE related to treatment, at least one serious AE (according to pharmacovigilance), at least one serious AE related to treatment will be described by treatment arm. A listing of serious AEs will be published
Measured: Inclusion, every 4 months for 2 years and then every 6 months until death or progression, assessed up to 36 months of follow-up from the last patient enrolled or until the 120th event occurs (wichever comes first)
Quality of Life (QoL)
QoL, will be assessed using the EORTC QLQ-C30 and the EORTC QLQ-ELD14 for the patients ≥ 75 years of age. The difference between the scores at inclusion and during follow-up will be calculated per patient. A difference of 10 points on each score will be considered clinically relevant. A graphic representation in the form of a spider plot will allow to globally visualize the evolution on all the items between the different measurement times.
Measured: Inclusion, every 4 months for 1 year, assessed up to 36 months of follow-up from the last patient enrolled or until the 120th event occurs (wichever comes first)
Interest of radiotherapy in the subgroup of patients over 75 years old
Due to the stratification, the aged population will be well distributed in a balanced way between the treatment arms. The main efficacy criterion and quality of life of this subpopulation will be studied in more detail.
Measured: Inclusion, every 4 months for 2 years and then every 6 months until death or progression, assessed up to 36 months of follow-up from the last patient enrolled or until the 120th event occurs (wichever comes first)
Interest of radiotherapy in the subgroup of patients with Perineural Neoplastic Invasion (PNI)
Due to the stratification, the population with PNI will be well balanced among the treatment arms. The main efficacy criterion and quality of life of this subpopulation will be studied in more detail.
Measured: Inclusion, every 4 months for 2 years and then every 6 months until death or progression, assessed up to 36 months of follow-up from the last patient enrolled or until the 120th event occurs (wichever comes first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2024
- Study start21 Feb 2025
- Primary completionJun 2031 (estimated)
- Study completionJun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous Squamous Cell Carcinoma (CSCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Masking
- None (open label)
- Enrolment
- 266 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Leon Berard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mona AMINI-ADLE, Dr, Principal investigator, Centre Leon Berard
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06692556
- Sponsor's protocol ID
- SPINO-RT (ET24-046)
- Acronym
- SPINO-RT
- Status last verified
- Apr 2026
- First submitted
- 14 Nov 2024
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No