Stereotactic Ablative Body Radiotherapy (SABR) Combined with Immunotherapy (L19-IL2) in Stage IV NSCLC Patients, ImmunoSABR: a Multicentre, Randomised Controlled Open-label Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 88
- 试验地点
- 15
- 主要终点
- Progression-free survival
研究概览
简要总结
This will be a phase II trial testing if the combination of stereotactic ablative body radiotherapy (SABR) and L19-IL2 improve the progression-free survival in patients with limited metastatic non-small cell lung cancer (NSCLC). The trial consists of one cohort with two arms; C-arm and an E-arm.
Patients with oligometastatic disease will receive SABR to minimal 1 and max all metastatic sites (max 5 sites irradiated) and patients with diffuse metastatic lesions (6 to max 10) will receive radiotherapy to max 5 sites. In the experimental arm, immunotherapy will be given after irradiation.
详细描述
IMMUNOSABR will include 126 patients. In this single-stage controlled randomised open-label phase II trial, we aim to demonstrate an absolute increase in progression-free survival (primary endpoint). PFS will be determined as the time between randomisation and disease progression, according to RECIST 1.1, death due to any cause or last patient contact alive and progression-free. Patients will be randomized between control (no immunocytokine) and experimental arms (with immunocytokine L19-IL2) in a 1:1 ratio. The accrual period will be 29 months (or 2.41 years), and the minimum follow-up will be 18 months (or 1.5 years), making the total study duration 47 months. Comparison between control and experimental arms will be made using the Log-Rank statistic. This test for superiority will be one-sided with the desired type I error of 0.10 and power of 0.90.
Patients enrolled in the trial will be randomised into the control arm (C-arm) or experimental arm (E-arm).
- C-arm: Standard of Care (SOC) according to the local and national guidelines: (wait and see or surgery and/or chemotherapy and/or standard (symptomatic) radiotherapy and/or SABR, oligometastatic disease.
- E-arm: SABR (oligometastatic disease) or radiotherapy (diffuse disease) + L19-IL2 up to 6 cycles (+ aPD(L)1 if SOC)
The expected 1.5-year PFS is 15% in the C-arm and 35% in the E-arm. A sample size of 116 patients (58 patients per treatment arm) is needed to show this difference of 20% in PFS, using a logrank test with a two-sided alpha of 0.05 and power of 85%. Patients will be evenly divided over the two arms. Assuming a drop-out rate of 10%, a total of 126 patients (63 per arm) need to be included.
Primary objective The main objective of the trial is to test if the activity of the combination of (SAB)R and L19-IL2 in patients with metastatic NSCLC will result in improved progression-free survival (PFS) compared to the SOC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Control
Standard of Care (SOC) according to the local and national guidelines: (wait and see or surgery and/or chemotherapy and/or standard (symptomatic) radiation therapy and/or SABR (oligometastatic disease)
干预措施: Radiation (Radiation)
Experimental treatment
Standard of Care (SOC SABR (oligometastatic disease) or radiation therapy (diffuse disease) + L19-IL2 up to 6 cycles (Darleukin)
干预措施: Darleukin (Drug)
Experimental treatment
Standard of Care (SOC SABR (oligometastatic disease) or radiation therapy (diffuse disease) + L19-IL2 up to 6 cycles (Darleukin)
干预措施: Radiation (Radiation)
结局指标
主要结局
Progression-free survival
时间窗: 18 months after randomization of the last patient
The main objective of the trial is to test the hypothesis that the combination of (SAB)R and L19-IL2 in patients with metastatic NSCLC will resulting in improved progression-free survival (PFS) compared to the SOC.
次要结局
- Change in out of field radio-immune (OFRI) response(at 3, 6, 9, 12, 15, 18, 21, 24 months after treatment)
- Immunoresponse blood biomarkers by enzyme-linked immunosorbent assay (ELISA)(baseline and at 3, 6 and 9 months after treatment)
- Overall survival(18 months after randomization of the last patient)
- Change in score of The EORTC quality of life questionnaire (QLQ) core module (C30)(baseline and at 3, 6, 9, 12, 15, 18, 21, 24 months after treatment)
- Change in score of The EORTC quality of life questionnaire (QLQ) - Lung cancer module (LC13)(baseline and at 3, 6, 9, 12, 15, 18, 21, 24 months after treatment)
- Change in score of The Euro Quality of Life (EQ) visual analogue scale (VAS)(baseline and at 3, 6, 9, 12, 15, 18, 21, 24 months after treatment)
- Change in score of The Euro Quality of Life - 5 dimensions - 5 levels (EQ-5D-5L)(baseline and at 3, 6, 9, 12, 15, 18, 21, 24 months after treatment)