Metastasis From Malignant Melanoma of Skin (Diagnosis)
Conditions
Keywords
FLASH therapy, melanoma
Brief summary
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.
Interventions
DEVICEFLASH therapy
Dose escalation of high dose rate radiotherapy (FLASH therapy) as single dose treatment for skin melanoma metastases that progress locally despite systemic treatments.
Sponsors
Centre Hospitalier Universitaire Vaudois
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed study Informed Consent Form 2. Karnofsky Performance Status (KPS) ≥ 50 3. Age ≥ 18 years 4. Patients with metastatic melanoma and multiple skin metastases with a documented clinical progression despite the systemic treatments (chemotherapy, and/or Programmed cell death 1 (PD1), cytotoxic T-lymphocyte antigen-4 (CTLA4) inhibitors or tyrosine kinase inhibitors (TKIs), such as v-raf murine sarcoma viral oncogene homolog B1 (BRAF) or mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors) 5. The size of the treated lesions should be ≤ 5.5 cm in diameter and ≤ 2.8 cm thick (caliper-based measurement) 6. The treated lesions should be at least 5 cm apart and must not be located on the face. 7. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (urine or serum) during screening 8. WOCBP must use a contraceptive method
Exclusion criteria
1. Previous radiotherapy in the treated area 2. Concomitant auto-immune disease with skin lesions 3. Concomitant use of radio-sensitizer drug 4. Women who are pregnant 5. Current, recent (within 10 days prior start of study treatment), or planned participation in an experimental drug study. During the 4 weeks DLT period, the patient will not be able to participate to any other clinical study. 6. Any serious underlying medical condition that could interfere with study treatment and potential adverse events 7. Any mental or other impairment that may compromise compliance with the requirements of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of maximum tolerated dose (MTD) or recommended phase II dose (RP2D), separately for skin metastases of small and large volumes. | from Day 1 to Day 28 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with Hemorrhage related to the treated lesions, assessed visually by the investigator | At each visit, from screening to 12 months post-treatment | Hemorrhage will be visually assessed (presence/abscence) |
| Percentage of patients with Skin ulceration related to the treated lesions, assessed visually by the investigator | At each visit, from screening to 12 months post-treatment | Skin ulceration will be visually assessed (presence/abscence) |
| Percentage of patients with Pain related to the treated lesions, assessed with analogic visual pain scale | At each visit, from screening to 12 months post-treatment | Pain will be assessed using an analogic visual pain scale (score from 1 to 10) |
| Local response of metastases in the radiation field, measured with calipers | 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 | 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. |
| Blinded Imaging Central Review (BICR) of photographs evaluating both tumor response and in radiation field normal tissue responses around the treated tumors | From Day 1 up to 12 months post-treatment | 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. |
| Optical coherence tomography (OCT) examination of the irradiated skin compared to the normal non-irradiated skin | at 4 weeks, 6 months and 12 months post-treatment | 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 |
| Frequency of late adverse events (within 12 months post-treatment) for each dose | within 12 months post-treatment | Long-term safety of RT procedure will be measured as recording of late adverse events (CTCAE v5.0) |
| Frequency of Late side effects observed in radiation field | ≥ 6 months post-treatment | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | within 12 months post-treatment (at 1, 3, 4, 6 weeks post-treatment; at 3, 6, 12 months post-treatment; at progression) | 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 |
Countries
Switzerland
Contacts
Primary ContactLana Kandalaft, Pharm D, PhD
Outcome results
None listed