A Phase I Clinical Study on Feasibility and Toxicity of LINAC-based Flash Radiotherapy for Palliative Treatment of Skin Lesions of Malignant Melanomas

Brief Summary

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.

Primary Outcomes

Secondary Outcomes

• Local response assessment(9 months)
• Relief of Pain(21 months)
• Relief of Hemorrhage(21 months)
• Late side effects(21 months)