Flash Radiotherapy for Skin Cancer

Phase 2Not Yet RecruitingNCT07455331

Jules Bordet Institute60 enrolled

Overview

The goal of this clinical investigation is to describe and compare the toxicity and efficacy of an experimental radiotherapy, named FLASH therapy, to conventional radiotherapy for subjects suffering from localized Cutaneous Squamous Cell Carcinoma (cSCC) and Basal Cell Carcinoma (BCC). FLASH therapy can deliver the irradiation dose within milliseconds instead of the minutes commonly required in conventional radiotherapy, with the aim of providing a curative dose while minimizing side effects on healthy tissue. This is a phase II selection and monocentric clinical investigation with a 1 to 1 randomization. This clinical investigation will include approximately 60 participants aged ≥ 60 years old with one or more localized cSCC and BCC who either cannot undergo surgery or decline surgical resection. The study design is the following: * On day 1, either a single dose FLASH radiotherapy (22 Gy) will be delivered or a single dose conventional radiotherapy (22 Gy) will be delivered to the selected localized cSCC or BCC lesion(s) (up to maximum 3 per participant; all lesions distant of at least 4 cm from one-another). * The surveillance period will be of 6 weeks post irradiation. * Follow-up visits will take place at 3, 6, and 12 months post-treatment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Cutaneous Squamous Cell Carcinoma (CSCC)

Eligibility

Sex: ALLMin age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signed study Informed Consent Form 2. Karnofsky Performance Status (KPS) ≥ 60 3. Age ≥ 60 years 4. Participants with histologically proven cSCC; or participants with BCC either histologically proven or proven by non-invasive imaging: either OCT, LC-OCT or RCM 5. Participants requiring radiotherapy treatment according to the dermato-oncology tumor board: participants who cannot undergo surgical procedure or participants who decline surgical resection, and/or anatomical locations where surgery can compromise function or cosmesis. 6. T1-N0 lesions (TNM UICC, 8th Edition) 7. Lesions should be at least 4 cm apart if treated with 2 different modalities (including surgical treatment of lesions). Lesions should not be located on the face, except on the forehead, above a line situated 1 cm above the eyebrows. Lesions located on the scalp can be treated 8. In cases of prior intervention within the target area, the treated lesion must be located at a distance of \> 4 cm from the previous site. Exclusion Criteria: 1. Previous radiotherapy in the treated area or a history of radiation therapy within 4 cm of the lesion to be treated 2. Concomitant auto-immune disease with skin lesions 3. Concomitant use of radio-sensitizer drug 4. Cognitive disorders not compatible with the signature of informed consent or that may compromise compliance with the requirements of the study 5. Current, recent (within 10 days prior to start of study treatment), or planned participation in an experimental drug study (before EOT visit) 6. Concomitant use of systemic or immunochemotherapy for skin cancer(s) 7. Concomitant use of systemic chemotherapy for a cancer other than the skin cancer(s) 8. Topical antitumoral treatment is prohibited within the radiation field except after a mandatory 4-weeks washout period. 9. Any active cutaneous infection within the irradiation field (except if completely resolved prior to the initiation of radiotherapy). 10. Uncontrolled intercurrent comorbidities that may impair wound healing including Diabetes Mellitus (HbA1c \> 8.5% or evidence of active diabetic ulceration), Chronic Venous Insufficiency with active venous ulcers, or severe (Grade 3+) oedema in the treatment field.

Outcomes

Primary Outcomes

Evaluate the safety of FLASH radiotherapy

Safety of FLASH radiotherapy measured by the collection of ≥ grade 3 skin toxicity AEs (CTCAE v6.0) ≤ 6 weeks after radiotherapy. Assessment will be performed by physical examination at 3,4,6 weeks post treatment (It may be necessary to perform these procedures at unscheduled time points if deemed clinically necessary by the investigator).

Time frame: "From enrollment until 6 weeks after radiotherapy"

hierarchically tested efficacy of FLASH radiotherapy

Hierarchically tested efficacy measured by local control rate at 1-year. Local control rate is censured by any in field local relapse up to one-year post randomization (Tumor response evaluated during physical exam). Assessment will be performed by physical exam and Blinded Imaging Central Review (BICR) of photographs at 3,4,6 weeks and 3,6,12 months.

Time frame: "From enrollment until 1-year post randomization"

Secondary Outcomes

Evaluate tumor response

Tumor response Assessment will be performed by physical exam and Blinded Imaging Central Review (BICR) of photographs at 3,4,6 weeks and 3,6,12 months post treatment

Time frame: "From enrolment until 12 months post-treatment"

Evaluate acute side effects "in the radiation field"

Acute side effects "in the radiation field" defined by any toxicity (CTCAE v6.0), until 3 months after the irradiation date. Assessment will be performed by physical exam, Blinded Imaging Central Review (BICR) of photographs at 3,4,6 weeks post treatment and OCT (optical coherence tomography) at 4 weeks post treatment.

Time frame: "From enrollment until 6 weeks after the irradiation date"

Evaluate late side effects "in the radiation field"

Late side effects "in the radiation field" (within 3 to 12 months post-treatment) (CTCAE v6.0). Assessment will be performed by physical exam, Blinded Imaging Central Review (BICR) of photographs 3,6,12 months post treatment and OCT (optical coherence tomography) at 6 and 12 months.

Time frame: "From 3 months post treatment until 12 months post treatment"