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
Overview
- Phase
- Phase 3
- Intervention
- Adjuvant radiotherapy
- Conditions
- Cutaneous Squamous Cell Carcinoma (CSCC)
- Sponsor
- Centre Leon Berard
- Enrollment
- 266
- Locations
- 50
- Primary Endpoint
- Disease-Free Survival (DFS)
- Status
- Recruiting
- Last Updated
- 8 days ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients aged ≥ 18 years at the time of signing the informed consent form; I
- •Patients with histologically confirmed localized cutaneous squamous cell carcinoma;
- •Note: Patients with carcinoma of the external auditory canal may be included in the study;
- •Patients treated with complete surgical excision (R0), regardless of the margin (submillimeter or supramillimeter);
- •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;
Exclusion Criteria
- •Patients with in situ or mixed CEC; NI
- •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; NI
- •History of CEC treated with systemic therapy; NI
- •Patients with SCC localized to the endonasal, intraoral, anogenital, or vulvar mucosa;
- •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). NI
- •Patients with CEC presenting a single risk factor other than EPN; NI
Arms & Interventions
Adjuvant radiotherapy
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.
Intervention: Adjuvant radiotherapy
Surveillance
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.
Outcomes
Primary Outcomes
Disease-Free Survival (DFS)
Time Frame: Up to 54 months
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.
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
- Local recurrence-free survival (lrFS)(Up to 54 months)
- Metastatic recurrence-free survival (mFS)(Up to 54 months)
- Overall Survival (OS)(Up to 54 months)
- Tolerance/toxicity(Up to 54 months)
- Quality of Life (QoL)(Up to 54 months)
- Interest of radiotherapy in the subgroup of patients over 75 years old(Up to 54 months)
- Interest of radiotherapy in the subgroup of patients with Perineural Neoplastic Invasion (PNI)(Up to 54 months)
- Local recurrence-free survival (lrFS)(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)(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)(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)(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(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)(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(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)(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))