Irradiation of Melanoma in a Pulse

Centre Hospitalier Universitaire Vaudois46 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastasis From Malignant Melanoma of Skin (Diagnosis)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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).

Time frame: from Day 1 to Day 28

Secondary Outcomes

Percentage of patients with Hemorrhage related to the treated lesions, assessed visually by the investigator

Hemorrhage will be visually assessed (presence/abscence)

Time frame: 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

Skin ulceration will be visually assessed (presence/abscence)

Time frame: 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)

Time frame: 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.

Time frame: 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"

Time frame: ≥ 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.

Time frame: 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

Time frame: 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)

Time frame: within 12 months post-treatment

Irradiation of Melanoma in a Pulse

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts