Multinational, randomized, controlled, open-label, multicenter phase II trial. Eligible patients will be randomized in a ratio of 1:1 to Experimental Arm (FDG-PET-based small volume accelerated radiotherapy with concurrent standard of care chemotherapy) or Conventional Arm (standard FDG-PET-based radiotherapy with concurrent standard of care chemotherapy). Patients showing complete response, partial response, or stable disease following chemoradiotherapy will receive standard of care consolidation therapy with durvalumab (fixed dose of 1500 mg q4w) for up to 12 months or until progression of disease, unacceptable toxicity, patient´s wish, or investigator´s decision, whichever comes first. After end of durvalumab therapy, patients will undergo safety follow up for 90 (+7) days followed by survival follow up until overall end of study. Overall end of study will be reached 24 months after the last patient has started durvalumab therapy. Patients showing PD following chemoradiotherapy will be treated according to investigator´s decision but will be followed up until overall end of study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
110
standard FDG-PET-based radiotherapy
concurrent standard of care chemotherapy
standard of care consolidation therapy with durvalumab (fixed dose of 1500 mg q4w) for up to 12 months or until progression of disease, unacceptable toxicity, patient´s wish, or investigator´s decision, whichever comes first.
FDG-PET-based small volume accelerated radiotherapy
Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden
Dresden, Germany
RECRUITINGUniversitätsklinikum Essen - Klinik für Strahlentherapie
Essen, Germany
NOT_YET_RECRUITINGMedical Center - University Of Freiburg, Department of Radiation Oncology
Freiburg im Breisgau, Germany
RECRUITINGUniversitätsmedizin Göttingen, Department for Radiotherapy and Radiooncology
Göttingen, Germany
RECRUITINGUniversität des Saarlandes, Klinik für Strahlentherapie und Radioonkologie
Homburg, Germany
RECRUITINGKliniken Maria Hilf GmbH Mönchengladbach
Mönchengladbach, Germany
RECRUITINGKlinikum der Universitaet Muenchen AöR, Department of Radiotherapy and Radiation Oncology
München, Germany
RECRUITINGPius-Hospital Oldenburg, Hematology and Oncology
Oldenburg, Germany
RECRUITINGVinzenz Von Paul Kliniken gGmbH, Klinik für Strahlentherapie und Palliativmedizin
Stuttgart, Germany
RECRUITINGÜberörtliche Berufsausübungsgemeinschaft Troisdorf
Troisdorf, Germany
RECRUITING...and 1 more locations
Comparison of the Completion rate of Experimental Arm to Conventional Arm
To assess the feasibility of an FDG-PET-based small volume accelerated chemoradiotherapy followed by immunotherapy with durvalumab compared to standard FDG-PET-based chemoradiotherapy followed by immunotherapy with durvalumab Completion rate defined as rate of patients having received: * the prescribed radiotherapy dose ± 2 fractions and * simultaneous platinum-based chemotherapy and · immunotherapy consolidation with durvalumab starting within 42 days after the last dose of chemoradiotherapy and * either at least 3 doses of durvalumab or less than 3 doses of durvalumab in case immunotherapy was permanently discontinued due to documented extrathoracic immune-related toxicity.
Time frame: approximately 22 weeks after start of radio-chemotherapy
Comparison of the Occurrence of adverse events and serious events of Experimental Arm to Conventional Arm
To assess the safety and tolerability of an FDGPET- based small volume accelerated chemoradiotherapy followed by immunotherapy with durvalumab compared to standard FDG-PET-based chemoradiotherapy followed by immunotherapy with durvalumab Occurrence of adverse events and serious events: * adverse events grade ≥ 3 (according to NCI CTCAE v5.0) * SAEs * Unexpected AEs
Time frame: up to 78 weeks
Comparison of the Time to locoregional progression of Experimental Arm to Conventional Arm
Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress \- Time to locoregional progression
Time frame: time from randomization to progression in the primary tumor or any of mediastinal lymph nodes, up to 143,5 weeks
Comparison of the Time to locoregional in-RT-field progression of Experimental Arm to Conventional Arm
Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress · Time to locoregional in-RT-field progression
Time frame: time from rando to progression in primary tumor or mediastinal lymph nodes within the target volume, up to 143,5 weeks
Comparison of the Time to locoregional out-of-RT-field progression of Experimental Arm to Conventional Arm
Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress · Time to locoregional out-of-RT-field progression
Time frame: time from rando to progression in mediastinal lymph nodes outside the target volume, up to 143,5 weeks
Comparison of the Time to distant progression time from rando to appearance of metastases elsewhere of Experimental Arm to Conventional Arm
Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress · Time to distant progression time from rando to appearance of metastases elsewhere
Time frame: time from rando to appearance of metastases elsewhere, up to 143,5 weeks
Comparison of the PFS of Experimental Arm to Conventional Arm
Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress · PFS
Time frame: time from rando to disease progression or death by any cause, up to 143,5 weeks
Comparison of the OS of Experimental Arm to Conventional Arm
Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress · OS
Time frame: time from rando to death by any cause, up to 143,5 weeks
Comparison of the ORR of Experimental Arm to Conventional Arm
Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress · ORR
Time frame: Objective response rate defined as the proportion of randomized patients with best response of complete or partial response, up to 143,5 weeks
Comparison of the DCR of Experimental Arm to Conventional Arm
Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress · DCR
Time frame: Disease control rate defined as the proportion of rando patients with best response of complete response, partial response, or stable disease, up to 143,5 weeks
Comparison of the Change in symptoms of Experimental Arm to Conventional Arm
Assess symptoms and patient-reported QoL in patients receiving an FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to patients receiving standard FDG-PET-based CRT followed by immunotherapy 1. Change in symptoms assessed with the EORTC QLQ-C30 2. Change in symptoms assessed with the EORTC QLQ-LC13 The results of the questionnaire are usually presented as scale scores, ranging from 0 to 100. Higher scores on the symptom scales indicate a worse quality of life.
Time frame: up to 143,5 weeks
Comparison of the Change in functioning of Experimental Arm to Conventional Arm
Assess symptoms and patient-reported QoL in patients receiving an FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to patients receiving standard FDG-PET-based CRT followed by immunotherapy 1. Change in functioning assessed with the EORTC QLQ-C30 2. Change in functioning assessed with the EORTC QLQ-LC13 The results of the questionnaire are usually presented as scale scores, ranging from 0 to 100. Higher scores on the functional scales indicate a better quality of life.
Time frame: up to 143,5 weeks
Comparison of the Change in global health-status/QoL of Experimental Arm to Conventional Arm
Assess symptoms and patient-reported QoL in patients receiving an FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to patients receiving standard FDG-PET-based CRT followed by immunotherapy 1. Change in global health-status/QoL assessed with the EORTC QLQ-C30 2. Change in global health-status/QoL assessed with the EORTC QLQ-LC13 The results of the questionnaire are usually presented as scale scores, ranging from 0 to 100. Higher scores on the global health and quality of life scale indicate a better quality of life.
Time frame: up to 143,5 weeks
To assure radiotherapy quality in terms of percentage of patients without major protocol deviations of ≥85%
Percentage of patients without major protocol deviations regarding radiotherapy quality
Time frame: up to 55 months
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