Clinical trial NCT04986696: Irradiation of Melanoma in a Pulse
Official title: A Phase I, First-in-human, Dose Finding Study of High Dose Rate Radiotherapy in Patients With Skin Metastases From Melanoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Metastasis From Malignant Melanoma of Skin (Diagnosis)
Keywords: FLASH therapy
melanoma
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
First posted: 2021-08-03
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation study
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Determination of maximum tolerated dose (MTD) or recommended phase II dose (RP2D), separately for skin metastases of small and large volumes.
timeFrame: from Day 1 to Day 28
Secondary outcomes:
measure: Percentage of patients with Hemorrhage related to the treated lesions, assessed visually by the investigator
timeFrame: At each visit, from screening to 12 months post-treatment
measure: Percentage of patients with Skin ulceration related to the treated lesions, assessed visually by the investigator
timeFrame: At each visit, from screening to 12 months post-treatment
measure: Percentage of patients with Pain related to the treated lesions, assessed with analogic visual pain scale
timeFrame: At each visit, from screening to 12 months post-treatment
measure: Local response of metastases "in the radiation field", measured with calipers
timeFrame: 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
measure: Frequency of Late side effects observed "in radiation field"
timeFrame: ≥ 6 months post-treatment
measure: Blinded Imaging Central Review (BICR) of photographs evaluating both tumor response and "in radiation field" normal tissue responses around the treated tumors
timeFrame: From Day 1 up to 12 months post-treatment
measure: Optical coherence tomography (OCT) examination of the irradiated skin compared to the normal non-irradiated skin
timeFrame: at 4 weeks, 6 months and 12 months post-treatment
measure: Frequency of late adverse events (within 12 months post-treatment) for each dose
timeFrame: within 12 months post-treatment
Other outcomes:
measure: 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
timeFrame: within 12 months post-treatment (at 1, 3, 4, 6 weeks post-treatment; at 3, 6, 12 months post-treatment; at progression)
Locations:
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
state: Vaud
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Jean Bourhis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.