A Phase I Dose-escalation Trial of Stereotactic Ablative Body Radiotherapy (SABR) for Non-spine Bone & Lymph Node Oligometastates
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Dose-limiting Toxicity
研究概览
简要总结
Stereotactic ablative body radiotherapy (SABR) can be considered for patients with so-called "oligometastatic" disease. However, since this is a relatively new technique, information on the optimal scheduling is lacking. Even prospective randomized trials on SABR for oligometastases typically allow different fractionation schedules to be used. This is especially true for non-spine bone and lymph node metastases, where the literature is scarce to non-existent.
There is also emerging evidence that SABR can stimulate the immune response, by a variety of mechanisms such as increasing TLR4 expression on dendritic cells, increasing priming of T cells in draining lymph nodes, and increasing tumor cell antigen presentation by dendritic cells. Again, it is not clear which fractionation schedule elicits the most robust immune response.
Therefore, it is opportune to compare the most commonly used stereotactic regimens regarding toxicity, efficacy, and immune priming.
This trial is a non-randomized prospective phase I trial determining a regimen of choice for patients with non-spine bone and lymph node oligometastases (≤ 3 lesions). The metastatic lesion(s) must be visible on CT and < 5 cm in largest diameter. A total of ninety patients will be consecutively included in three different fractionation regimens. They will be offered stereotactic ablative radiotherapy to all metastatic lesions in 5, 3 or 1 fractions. Dose-limiting toxicity (DLT), defined as any acute grade 3 or 4 toxicity, will be recorded as the primary endpoint. Overall acute and late toxicity, quality of life, local control, and progression-free survival are secondary endpoints.
Liquid biopsies will be collected throughout the course of this trial, i.e. at simulation, after each fraction and at 6 months after the end of the radiotherapy. Translational research will focus on assessment of circulating cytokines and flow cytometry analysis of immune cells.
详细描述
- Background & rationale
Stereotactic ablative body radiotherapy (SABR) is indicated in patients with oligometastatic, oligoprogressive, or traditionally radioresistant disease, who often present with minimal or no associated symptoms [1, 2]. However, since this is a relatively new technique, information on the optimal scheduling is lacking. Even prospective randomized trials on SABR for oligometastatic disease typically allow different fractionation schedules to be used [3]. This is especially true for non-spine bone and lymph node metastases, where the literature is scarce to non-existent and many different schedules are used, even within a single center [4,5].
There is also emerging evidence that SABR can stimulate the immune response, by a variety of mechanisms such as increasing toll-like receptor 4 (TLR4) expression on dendritic cells, increasing priming of T cells in draining lymph nodes, and increasing tumor cell antigen presentation by dendritic cells [6]. Again, it is not clear which fractionation schedule elicits the most robust immune response. For instance, in combination with cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) immunotherapy, different radiation regimens in two carcinoma models growing in syngeneic mice were compared [7]. Marked differences in induction of tumor-specific T cells and of an abscopal effect were observed. Each regimen had similar ability to inhibit the growth of the irradiated tumor when radiation was used alone. The addition of anti-CTLA-4, however, caused complete regression of the majority of irradiated tumors and an abscopal effect in mice receiving a hypofractionated regimen (3 fractions of 8 Gy) but not in mice treated with a single dose of 20 Gy. An additional fractionated regimen (5 fractions of 6 Gy) was tested, which showed intermediate results. This indicates that a specific therapeutic window may exist for the optimal use of radiotherapy as an immune adjuvant.
It seems an opportune moment to compare the most commonly used stereotactic regimens regarding toxicity and efficacy.
- Trial design
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
- •Patients ≥ 18 years old with histologically confirmed malignancy.
- •Patients with radiosensitive malignancy (e.g. breast, prostate,...) and oligometastases (i.e. ≤ 3 metastases) OR patients with radioresistant malignancy (e.g. renal cell carcinoma, melanoma,...) and an unlimited number of metastases.
- •Metastatic lesion must be visible on CT and < 5 cm in largest diameter.
- •Patients with ECOG performance status ≤
- •Patients who have received the information sheet and signed the informed consent form.
- •Patients must be willing to comply with scheduled visits, treatment plan, and other study procedures.
- •Patients with a public health insurance coverage.
排除标准
- •Patients with life expectancy < 6 months.
- •Patients with previous radiotherapy to the metastatic area excluding stereotactic re-irradiation to the required dose level.
- •Patients with significantly altered mental status or with psychological, familial, sociological or geographical condition potential hampering compliance with the study.
- •Individual deprived of liberty or placed under guardianship.
结局指标
主要结局
Dose-limiting Toxicity
时间窗: 6 months after SABR
To determine the maximum tolerated dose (MTD). The maximal tolerated dose will be defined as the dose level below which at least 10 patients present with a dose-limiting toxicity .
次要结局
- Late toxicities following SABR(at 9, 12, 18 and 24months after last day of SABR)
- Local control(at 6 months after last day of SABR)
- Progression-free survival(at 6 months after last day of SABR)
- Acute toxicities following SABR(at 3 and 6 months after last day of SABR)
研究者
Piet Dirix
Radiation Oncologist
Cancer Research Antwerp