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This is a single center phase I, first-in-human, dose escalation study of FLASH therapy in patients with metastases of melanoma.
The trial is based on escalating single doses of FLASH therapy administered to skin melanoma metastases using the Mobetron® with high dose rate (HDR) functionality.
The aim of the study is to evaluate a dose escalation of high dose rate radiotherapy (FLASH therapy) as single dose treatment for skin melanoma metastases that progress locally despite systemic treatments. Melanoma is a typically radio-resistant tumor type, which can justify such a dose escalation with a new type of radiotherapy that appears much better tolerated than conventional radiotherapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose escalation of FLASH therapy in skin metastases of small volume (≤ 30 cc) | Experimental | 7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy) |
|
| Dose escalation of FLASH therapy in skin metastases of large volume (> 30 and ≤ 100 cc) | Experimental | 7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FLASH therapy | Device | Dose escalation of high dose rate radiotherapy (FLASH therapy) as single dose treatment for skin melanoma metastases that progress locally despite systemic treatments. |
| Measure | Description | Time Frame |
|---|---|---|
| Determination of maximum tolerated dose (MTD) or recommended phase II dose (RP2D), separately for skin metastases of small and large volumes. | Acute safety (dose limiting toxicity, DLT) of the high dose rate radiotherapy (RT) procedure (for each dose level) will be evaluated during the 4 weeks post-treatment using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0). | from Day 1 to Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of patients with Hemorrhage related to the treated lesions, assessed visually by the investigator | Hemorrhage will be visually assessed (presence/abscence) | At each visit, from screening to 12 months post-treatment |
| Percentage of patients with Skin ulceration related to the treated lesions, assessed visually by the investigator |
| Measure | Description | Time Frame |
|---|---|---|
| Observation of a potential Abscopal Effect with evidence of tumor regression on metastases outside of the radiation field, measured with a caliper for cutaneous lesion or on radiological images for other lesions | Observation of a potential Abscopal Effect with evidence of tumor regression on metastases outside of the radiation field, measured with a caliper for cutaneous lesion or on radiological images for other lesions |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lana Kandalaft, Pharm D, PhD | Contact | +41 21 314 78 23 | lana.kandalaft@chuv.ch |
| Name | Affiliation | Role |
|---|---|---|
| Jean Bourhis, MD, PhD | Centre Hospitalier Universitaire Vaudois | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Universitaire Vaudois (CHUV) | Recruiting | Lausanne | Canton of Vaud | 1011 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35736814 | Derived | Maity A, Koumenis C. Shining a FLASHlight on Ultrahigh Dose-Rate Radiation and Possible Late Toxicity. Clin Cancer Res. 2022 Sep 1;28(17):3636-3638. doi: 10.1158/1078-0432.CCR-22-1255. |
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| ID | Term |
|---|---|
| D004194 | Disease |
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
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Dose escalation study
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|
Skin ulceration will be visually assessed (presence/abscence) |
| At each visit, from screening to 12 months post-treatment |
| Percentage of patients with Pain related to the treated lesions, assessed with analogic visual pain scale | Pain will be assessed using an analogic visual pain scale (score from 1 to 10) | At each visit, from screening to 12 months post-treatment |
| Local response of metastases "in the radiation field", measured with calipers | Irradiated lesions will be measured with calipers. Local response of metastases in the radiation field will be calculated as rate over all treated lesions and will be compared between small versus large volume lesions within each dose level. | At screening, Day 1, at weeks 1, 3, 4, and 6 post-treatment; at months 3, 6, and 12 post-treatment; and at local progression |
| Frequency of Late side effects observed "in radiation field" | ≥ 6 months post-treatment |
| Blinded Imaging Central Review (BICR) of photographs evaluating both tumor response and "in radiation field" normal tissue responses around the treated tumors | A baseline photograph will be taken the day of the treatment in a pre-therapeutic setting with skin delineation of the lesion. Then photos will be repeated at 1 (+/-2d), 3 (+/-2d), 4 (+/-3d), 6 (+/-3d) weeks after treatment, then at 3 (+/-7d), 6 (+/-14d), 12 (+/-14d) months and at progression. | From Day 1 up to 12 months post-treatment |
| Optical coherence tomography (OCT) examination of the irradiated skin compared to the normal non-irradiated skin | Epidermis thickness and roughness; plexus depth; number and size of vessels; number and size of hairs, will be compared between irradiated skin and normal non-irradiated skin | at 4 weeks, 6 months and 12 months post-treatment |
| Frequency of late adverse events (within 12 months post-treatment) for each dose | Long-term safety of RT procedure will be measured as recording of late adverse events (CTCAE v5.0) | within 12 months post-treatment |
| within 12 months post-treatment (at 1, 3, 4, 6 weeks post-treatment; at 3, 6, 12 months post-treatment; at progression) |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |