This is a randomized, open-label, multicenter, phase II trial investigating the combination of thoracic radiotherapy plus Durvalumab in patients with locally advanced, unresectable NSCLC (stage III) that are unfit for chemotherapy (e.g. due to age and/or frailty).
This trial investigates the feasibility and treatment efficacy when combining durvalumab treatment with either conventionally fractionated (CON-group) or hypofractionated thoracic radiotherapy (HYPO-group) in previously untreated NSCLC stage III patients prone to radiotherapy only. A safety lead-in phase with stop-and-go design will precede full enrollment into the HYPO-group. Tumor tissue as well as blood and stool samples will be collected for future biomarker analysis. It is hypothesized that TRT combined with concurrent durvalumab administration in patients with unresectable stage III NSCLC, who are not amenable to sequential radio-/chemotherapy 1. is safe and feasible, 2. will improve treatment efficacy by a synergistic effect of checkpoint inhibition and the photon-induction of immunostimulatory pathways. 3. will have an effect on the immunological characteristics of the tumor, the microenvironment, and the systemic immune response, such as upregulation of PD-L1 or secretion of stimulatory cytokines and recruitment and priming of immunocompetent cells, which might then mediate the "abscopal effect" beyond the irradiated targets.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
51
Durvalumab fixed dose of 1,500 mg
Conventionally fractionated TRT consisting of 30 x 2 Gy (60 Gy) within 6 weeks
Hypofractionated TRT consisting of 20 x 2,75 Gy (55 Gy) within 4 weeks
Universitätsklinikum Aachen
Aachen, Germany
DRK Kliniken Berlin-Mitte
Berlin, Germany
Kliniken der Stadt Köln gGmbH, Lungenklinik Merheim
Cologne, Germany
Toxicity (pneumonitis)
Toxicity, defined by the occurence of treatment-related pneumonitis grade ≥ 3
Time frame: up to 35 months
Objective response
Objective response evaluated at 12 weeks (3 months) after first durvalumab administration according to RECIST 1.1 criteria
Time frame: up to 35 months
treatment-related AEs and SAEs
Occurence of treatment-related AEs and SAEs according to CTCAE V5.0
Time frame: up to 35 months
frequency of abnormal laboratory parameters (hematology panel, chemistry panel, Thyroid-stimulating hormone (TSH))
Frequency of abnormal values of laboratory parameters
Time frame: up to 35 months
Progression Free Survival (PFS)
PFS according to RECIST 1.1
Time frame: up to 35 months
Duration of Clinical Benefit
Duration of Clinical Benefit (Duration of Complete Response (CR), Partial Response (PR), Stable Disease (SD)) according to RECIST 1.1
Time frame: up to 35 months
Metastasis-Free Survival (MFS)
Time from the date of allocation / randomization to the date of first observed metastatic lesion (investigator assessment according to RECIST 1.1) or death from any cause
Time frame: up to 35 months
Overall survival
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Universitätsmedizin Göttingen
Göttingen, Germany
Onkodok GmbH
Gütersloh, Germany
Thoraxklinik am Universitätsklinikum Heidelberg
Heidelberg, Germany
Lungenklinik Hemer, Pneumologie und Thorakale Onkologie
Hemer, Germany
Vincentius-Diakonissen-Kliniken gAG
Karlsruhe, Germany
Klinikum Ludwigsburg
Ludwigsburg, Germany
Universitätsmedizin Mainz
Mainz, Germany
...and 4 more locations
time from the date of treatment allocation to the date of death
Time frame: up to 35 months
Quality of Life (FACT-L)
measured by FACT-L questionnaire
Time frame: up to 35 months
objective response rate
Descriptive sub-group analyses of efficacy in relation to PD-L1 expression levels (\<°1% vs ≥°1%)
Time frame: up to 35 months