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NCT Number: 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

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

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Key information

Conditions

Cutaneous Squamous Cell Carcinoma (CSCC)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centre Hospitalier Emile Roux, Le Puy-en-Velay, Auvergne-Rhône-Alpes, France

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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;
  • 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).

Exclusion criteria

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.

Treatment and study plan

Adjuvant radiotherapy

Radiation

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.

Primary outcomes

  1. Disease-Free Survival (DFS)

    Time frame: 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)

    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.

Secondary outcomes

  1. Local recurrence-free survival (lrFS)

    Time frame: 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)

    lrFS is defined as the time from randomization (or surgery) to the first occurrence of regional recurrence or death from any cause.

  2. Regional Recurrence-Free Survival (RrFS)

    Time frame: 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)

    RrFS is The time from randomization (or surgery) to the first occurrence of regional recurrence or death from any cause, whichever came first

  3. Metastatic recurrence-free survival (MrFS)

    Time frame: 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)

    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.

  4. Overall Survival (OS)

    Time frame: 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

    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.

  5. Tolerance/toxicity

    Time frame: 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)

    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

  6. Quality of Life (QoL)

    Time frame: 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)

    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.

  7. Interest of radiotherapy in the subgroup of patients over 75 years old

    Time frame: 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)

    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.

  8. Interest of radiotherapy in the subgroup of patients with Perineural Neoplastic Invasion (PNI)

    Time frame: 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)

    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.

Other outcomes

  1. Progression-free survival after loco-regional recurrence salvage therapy in the Surveillance group

    Time frame: 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Julien GAUTIER

CONTACT

[email protected]

+33 4.26.55.68.29

Sponsors and collaborators

Lead sponsor

Centre Leon Berard

Other

Registry information

Official study 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

Acronym: SPINO-RT

Important dates

Study start
2025
Primary completion
2031
Study completion
2031
First posted
Nov 18, 2024
Registry last updated
Apr 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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