Ignite Creation Date:
2025-12-24 @ 7:45 PM
Ignite Modification Date:
2025-12-30 @ 9:50 AM
Study NCT ID:
NCT03705403
Status:
TERMINATED
Last Update Posted:
2025-01-30
First Post:
2018-06-27
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
IMMUNOtherapy and Stereotactic ABlative Radiotherapy (IMMUNOSABR) a Phase II Study
Sponsor:
Maastricht University Medical Center
Organization:
Study Overview
Official Title:
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
Status:
TERMINATED
Status Verified Date:
2025-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
This trial is not transitioning to the Clinical Trial Regulation (CTR) EU No 536/2014.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IMMUNOSABR2
Brief Summary:
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.
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.
Detailed Description:
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.
Secondary Objectives
* Assessment of the PFS of the patient cohort, at 5 years after randomisation.
* Assessment of the overall survival of the patient cohort, at 5 years after randomisation.
* To assess the toxicity of this treatment schedule;
* To assess Quality of Life (QoL);
* To assess the occurrence of an Out of Field Radio-Immune (OFRI) response / abscopal effect using imaging;
* To assess the occurrence of an In Field Radio-Immune (IFRI) response using imaging;
* To perform correlative biomarker studies related to treatment response.
Exploratory endpoints:
* Correlative biomarker studies:
* Tumour tissue: e.g EDB expression, non-synonymous mutations, immune monitoring;
* Blood: e.g. EDB expression, cfDNA, and immune monitoring;
* Radiomics on CT and if available MRI;
* Faeces: diversity in microbiota.
* iRECIST
* Tumour grow kinetics
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.
Secondary Objectives
* Assessment of the PFS of the patient cohort, at 5 years after randomisation.
* Assessment of the overall survival of the patient cohort, at 5 years after randomisation.
* To assess the toxicity of this treatment schedule;
* To assess Quality of Life (QoL);
* To assess the occurrence of an Out of Field Radio-Immune (OFRI) response / abscopal effect using imaging;
* To assess the occurrence of an In Field Radio-Immune (IFRI) response using imaging;
* To perform correlative biomarker studies related to treatment response.
Exploratory endpoints:
* Correlative biomarker studies:
* Tumour tissue: e.g EDB expression, non-synonymous mutations, immune monitoring;
* Blood: e.g. EDB expression, cfDNA, and immune monitoring;
* Radiomics on CT and if available MRI;
* Faeces: diversity in microbiota.
* iRECIST
* Tumour grow kinetics
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: