A Phase I, First-in-human, Dose Finding Study of High Dose Rate Radiotherapy in Patients With Skin Metastases From Melanoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Determination of maximum tolerated dose (MTD) or recommended phase II dose (RP2D), separately for skin metastases of small and large volumes.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed study Informed Consent Form
- •Karnofsky Performance Status (KPS) ≥ 50
- •Age ≥ 18 years
- •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)
- •The size of the treated lesions should be ≤ 5.5 cm in diameter and ≤ 2.8 cm thick (caliper-based measurement)
- •The treated lesions should be at least 5 cm apart and must not be located on the face.
- •Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (urine or serum) during screening
- •WOCBP must use a contraceptive method
排除标准
- •Previous radiotherapy in the treated area
- •Concomitant auto-immune disease with skin lesions
- •Concomitant use of radio-sensitizer drug
- •Women who are pregnant
- •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.
- •Any serious underlying medical condition that could interfere with study treatment and potential adverse events
- •Any mental or other impairment that may compromise compliance with the requirements of the study
结局指标
主要结局
Determination of maximum tolerated dose (MTD) or recommended phase II dose (RP2D), separately for skin metastases of small and large volumes.
时间窗: 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).
次要结局
- 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)
- 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)
- 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)
- Frequency of late adverse events (within 12 months post-treatment) for each dose(within 12 months post-treatment)
- 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(From Day 1 up to 12 months post-treatment)
- 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)
- 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)
研究者
Jean Bourhis
Prof., MD, PhD
Centre Hospitalier Universitaire Vaudois