EFLASH for Skin Lesions of Malignant Melanomas

Not Applicable

Recruiting

• Conditions: Metastatic Melanoma
• Interventions: Radiation: Electron FLASH radiotherapy

• Registration Number: NCT06549439
• Lead Sponsor: University of Zurich

Brief Summary

This prospective single center phase I trials aims to assess feasibility and safety of electron FLASH RT for treatment of melanoma skin metastases. Feasibility will be defined as FLASH delivery with an accuracy of +/-10% for each fraction, safety will be confirmed if a maximum of 2 out of 6 patients develop dose limited toxicity.

Detailed Description

Trial aim:

This prospective single center phase I trial aims to assess feasibility and safety of electron Flash RT for treatment of melanoma skin metastases. Feasibility will be defined as Flash delivery with an accuracy of ±10% for at least 10 out of 12 Flash-RT fractions and the accuracy of the total reference dose delivered (3x 9 Gy) is ±5%, safety will be confirmed if a maximum of 2 out of 6 patients develop dose-limiting toxicity.

Intervention Flash:

A nominal electron energy of 9 MeV will be used for both Flash-RT and Conv-RT, which guarantees ≥ 90% dose coverage up to a depth of 2.8 cm. Shallower lesions will be treated with the same electron energy and with a bolus. In order to treat these patients, field sizes between 2x2cm2 and 10x10cm2 will be used, which can be delivered with sufficient flatness (\<5%) and symmetry (\<2%) by the FlashTrueBeam v2.7.5.

Trial outline:

In the primary cohort, six patients with ≥ 1 melanoma skin lesion(s) (possible other lesions do not have to be treated) will be treated with a radiotherapy schedule of 3x 9 Gy (2x fractions/ week; α/β(3): EQD2: 64.8 Gy; α/β(10): EQD2: 42.75 Gy). A minimum of one lesion will be treated with Flash-RT (2x 9 Gy) and Conv-RT (1x 9 Gy) as experimental treatment and an optional minimum of one lesion will be treated with Conv-RT (3x 9 Gy) as "internal" control. As a consequence, also patients with a single lesion can be included into the trial. For the experimental treatment, the first two fractions will be applied with Flash-RT. Following dosimetry of these two fractions, the third fraction will be applied by Conv-RT and will be adjusted to compensate for possible lower or higher doses applied with Flash-RT before. This approach ensures that every lesion is treated with precisely a total reference dose of 27 Gy (± 5%), ultimately.

In an optional expansion cohort, up to 4 additional patients (total of n=10) will be recruited. The expansion cohort serves to further validate the primary results. The initiation of the expansion cohort requires to following three factors: 1. A maximum of 2 out of 6 patients develop DLT an no unexpected high-grade toxicity appear in the primary cohort; 2. Feasibility in the first six patients was shown (defined as Flash delivery with an accuracy of ±10% for at least 10 out of 12 Flash-RT fractions and the accuracy of the total reference dose delivered (3x 9 Gy) of ±5%); 3. No excessive duration in the recruitment of the primary cohort. Patients will be included and treated into the expansion cohort as in the primary cohort.

Study Timeline

• Study Start: 2024-01-22
• Study First Submitted: 2024-03-15
• Study First Submitted QC: 2024-08-07
• Study First Posted: 2024-08-12
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-24
• Last Update Posted: 2025-02-27
• Primary Completion: 2025-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	Electron FLASH radiotherapy	A nominal electron energy of 9 MeV will be used for both Flash-RT and Conv-RT, which guarantees ≥ 90% dose coverage up to a depth of 2.8 cm. Shallower lesions will be treated with the same electron energy and with a bolus. In order to treat these patients, field sizes between 2x2cm2 and 10x10cm2 will be used, which can be delivered with sufficient flatness (\<5%) and symmetry (\<2%) by the FlashTrueBeam v2.7.5.

Primary Outcome Measures

Name	Time	Method
Dose Accuracy (Feasibility)	9 months	H0: More than of 2 out of 12 Flash-RT fractions in the primary study cohort (n=6) have a dose deviation larger than ±10%.; H1: A maximum of 2 out of 12 Flash-RT fractions in the primary study cohort (n=6) have a dose deviation larger than ±10%.
Dose Limiting Toxicity (Safety)	9 months	H0: More than of 2 out of 6 patients in the primary study cohort (n=6) develop DLT in FLASH-irradiated lesions.; H1: A maximum of 2 out of 6 patients in the primary study cohort (n=6) develop DLT in FLASH-irradiated lesions.

Secondary Outcome Measures

Name	Time	Method
Local response assessment	9 months	Local response and control of irradiated metastases will be measured as recording of clinical response assessment including photo documentation
Relief of Pain	21 months	Pain will be assessed using an analogic visual pain scale (scale 0-10; 0=no pain, 10=worst pain)
Relief of Hemorrhage	21 months	Hemorrhage will be visually assessed by the investigator
Late side effects	21 months	Late side effects "in radiation field" (≥ 3 months an within 12 months post-treatment) will be measured as recording of late adverse events (CTCAE v5.0); and comparison of Flash- and Conv-irradiated lesions

Trial Locations

Locations (1)

University Hospital Zurich; 🇨🇭 Zurich, Switzerland