Ignite Creation Date:
2025-12-24 @ 7:57 PM
Ignite Modification Date:
2025-12-30 @ 2:05 PM
Study NCT ID:
NCT07111104
Status:
COMPLETED
Last Update Posted:
2025-08-08
First Post:
2025-07-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Survival Efficacy of Combined Radiotherapy and Immunotherapy in Patients With Metastatic Non-small Cell Lung Carcinoma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002289', 'term': 'Carcinoma, Non-Small-Cell Lung'}, {'id': 'D009362', 'term': 'Neoplasm Metastasis'}], 'ancestors': [{'id': 'D002283', 'term': 'Carcinoma, Bronchogenic'}, {'id': 'D001984', 'term': 'Bronchial Neoplasms'}, {'id': 'D008175', 'term': 'Lung Neoplasms'}, {'id': 'D012142', 'term': 'Respiratory Tract Neoplasms'}, {'id': 'D013899', 'term': 'Thoracic Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D009385', 'term': 'Neoplastic Processes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D007167', 'term': 'Immunotherapy'}, {'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D011878', 'term': 'Radiotherapy'}], 'ancestors': [{'id': 'D056747', 'term': 'Immunomodulation'}, {'id': 'D013812', 'term': 'Therapeutics'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 350}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2024-10-14', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2025-04-28', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-07-31', 'studyFirstSubmitDate': '2025-07-09', 'studyFirstSubmitQcDate': '2025-07-31', 'lastUpdatePostDateStruct': {'date': '2025-08-08', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-08-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-10-14', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Progression Free Survival (PFS)', 'timeFrame': 'Up to 18 months from start of immunotherapy', 'description': 'PFS is defined as the time from the first administration of immunotherapy to the date of confirmed disease progression or death from any cause, whichever occurs first. Progression is assessed using imaging (CT scan, PET scan or MRI) according to iRECIST v1.1 criteria.'}], 'secondaryOutcomes': [{'measure': 'Overall Survivall (OS)', 'timeFrame': 'Up to 18 months from start of immunotherapy', 'description': 'OS is defined as the time from the first administration of immunotherapy to the date of death from any cause.'}, {'measure': 'Objective Response Rate (ORR)', 'timeFrame': 'Up to 18 months from start of immunotherapy', 'description': 'ORR is defined as the best tumor response observed during treatment according to iRECIST v1.1 criteria.\n\nResponses are evaluated based on routine imaging (CT scan, PET scan or MRI) and classified into 5 categories: complete response (iCR), partial response (iPR), stable disease (iSD), unconfirmed progressive disease (iUPD) and confirmed progressive disease (iCPD).'}, {'measure': 'Objective Response Rate (ORR bis)', 'timeFrame': 'Up to 18 months from start of immunotherapy', 'description': 'ORR bis is defined in patients receiving both immunotherapy and radiotherpy and refers to the evaluation of the abscopal effect, i.e. tumor response in non-irradiated lesions according to iRECIST v1.1 criteria.\n\nResponses are evaluated based on routine imaging (CT scan, PET scan or MRI) and classified into 5 categories: complete response (iCR), partial response (iPR), stable disease (iSD), unconfirmed progressive disease (iUPD) and confirmed progressive disease (iCPD).'}, {'measure': 'Progression Free Survival 2 (PFS-2)', 'timeFrame': 'Up to 18 months from start of immunotherapy', 'description': 'PFS-2 is defined as the time from the start the therapy following immunotherapy to the date of confirmed disease progressipn or death from any cause, whichever occurs first.\n\nProgression is assessed using imaging (CT scan, PET scan or MRI) according to iRECIST v1.1 criteria.'}, {'measure': 'Progression Free Survival after Radiotherapy (PFS RT)', 'timeFrame': 'Up to 18 months from end of radiotherapy.', 'description': 'PFS-RT is defined as the time from the end of radiotherapy to the date of confirmed disease progression or death from any cause, whichever occurs first.\n\nProgression is assessed using imaging (CT scan, PET scan or MRI) according to iRECIST v1.1 criteria.'}, {'measure': 'Frequency and severity of toxicities of combined immunotherapy and radiotherapy, according to CTCAE v5.0 grades', 'timeFrame': 'Up to 18 months from start of immunotherapy', 'description': 'Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.\n\nGrade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL.\n\nGrade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care and activities of daily living (ADL).\n\nGrade 4 Life-threatening consequences; urgent intervention indicated.\n\nGrade 5 Death related to adverse events (AE).'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['non small cell lung cancer', 'NSCLC', 'metastatic', 'radiotherapy', 'immunotherapy'], 'conditions': ['Non Small Cell Lung Cancer Metastatic']}, 'descriptionModule': {'briefSummary': 'The aim of this retrospective, multicenter, observational study is to evaluate the potential clinical benefit of adding radiotherapy (administered either concomitantly or sequentially) to immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC).\n\nOne promising approach involves the integration of radiotherapy into the treatment plan. Radiotherapy is known not only for its cytotoxic local effects, but also for its ability to modulate the tumor microenvironment, increase antigen presentation, and stimulate systemic immune responses.\n\nThis study will compare two cohorts of patients with metastatic NSCLC treated in real-world clinical settings. The first cohort includes patients treated with immunotherapy alone, while the second includes those who received immunotherapy in combination with radiotherapy. Radiotherapy may have been administered concurrently or sequentially with respect to immunotherapy, based on clinical judgment.\n\nThe primary objective is to determine whether the addition of radiotherapy improves progression-free survival (PFS) by at least 30%, compared to immunotherapy alone. This threshold reflects clinically meaningful differences reported in randomized controlled trials in similar populations and treatment lines. Secondary objectives include overall survival (OS) and exploring predictive factors of treatment response, such as patient demographics, tumor characteristics, mutational status, timing of radiotherapy and abscopal effect evaluation, to refine patient selection for future combination strategies.\n\nEligible participants are adults with histologically confirmed metastatic NSCLC, treated with first-line or second-line immunotherapy, and with no prior exposure to immunotherapy. Data will be retrospectively collected from medical records, and treatment arms will be assigned based on actual clinical care paths.\n\nParticipants will:\n\n* Be retrospectively identified from hospital records.\n* Be assigned to one of two cohorts: immunotherapy alone or immunotherapy + radiotherapy (concomitant or sequential).\n* Have their data analyzed for OS, PFS, toxicity, and potential predictive biomarkers.\n\nThe results of this study will contribute to a better understanding of real-world outcomes in metastatic NSCLC patients and may inform future prospective trials evaluating radiotherapy as a modulator of immunotherapy efficacy.', 'detailedDescription': 'Metastatic non-small cell lung cancer (NSCLC) remains a highly heterogeneous disease with variable responses to immune checkpoint inhibitors, despite their transformative impact on patient outcomes since 2015. Radiotherapy has emerged as a potential synergistic partner for immunotherapy, based not only on its established local cytotoxic effects but also on its capacity to modulate the tumor microenvironment and activate systemic anti-tumor immunity.\n\nSeveral preclinical and early clinical studies have illustrated how radiation may increase tumor antigen release, upregulate MHC (Major Histocompatibility Complex) class I molecules, and enhance T-cell priming. The abscopal effect, while rare, underscores the possibility that localized radiotherapy can induce immune-mediated tumor regression at distant, non-irradiated sites. These observations support a growing rationale for combining immune checkpoint inhibitors with radiotherapy in a therapeutic strategy that goes beyond additive effects, aiming instead for immune potentiation.\n\nThis retrospective, multicenter, observational study investigates whether real-world integration of radiotherapy into immunotherapy regimens improves survival outcomes in patients with metastatic NSCLC. The study is designed to reflect routine clinical practices across participating institutions, with radiotherapy administration (either concomitant or sequential) guided by multidisciplinary clinical decision-making rather than protocolized intervention. This pragmatic approach allows for exploration of a wide range of clinical scenarios and patient profiles, including variation in timing, dose, target site, and sequence of the radiotherapy-immunotherapy combination.\n\nIn addition to comparing overall survival (OS) and progression-free survival (PFS) between patients treated with immunotherapy alone versus those receiving additional radiotherapy, the study also seeks to characterize patterns of treatment response, including tumor control in non-irradiated sites, and to identify subgroups most likely to benefit from the combination strategy. Particular interest lies in the immune effect beyond the radiation field, which could serve as an indirect marker of enhanced systemic immune activation.\n\nThis study not only aims to generate meaningful insights into real-world treatment patterns and outcomes but also to provide a foundation for future prospective clinical trials. By better understanding how radiotherapy might modulate the immunotherapeutic response in metastatic NSCLC, we hope to refine patient selection, optimize treatment timing, and ultimately improve the effectiveness of immunotherapy in this challenging clinical setting.\n\nData will be extracted retrospectively from medical records and institutional databases. Collected data will include:\n\n* Demographics: age, sex, smoking history\n* Clinical data: performance status, TNM stage (classification system for classifying malignancy), histology, PD-L1 (Programmed Cell Death Ligang 1) status\n* Immunotherapy details: agent, start date, treatment duration\n* Radiotherapy details: date, site, dose, technique, concurrent/sequential timing\n* Survival endpoints: OS (from start of immunotherapy to death), PFS (from start of immunotherapy to radiologic progression or death)\n* Adverse events graded by CTCAE (Commun Terminology Criteria for Adverse Events) criteria\n* Imaging reports and tumor response: RECIST v1.1 (Response Evaluation Criteria In Solid Tumor) or iRECIST\n\nStatistical Analyses:\n\n* Descriptive statistics: means, medians, frequencies\n* Kaplan-Meier analysis for OS and PFS\n* Cox proportional hazards regression for hazard ratio estimates\n* Subgroup analyses by timing of radiotherapy, PD-L1 level, and other covariates\n* Multivariate analysis adjusting for confounders A propensity score matching technique will be used to minimize selection bias by balancing key baseline characteristics between treatment groups. This will allow a more accurate estimation of the effect of radiotherapy, independent of potential confounders such as PD-L1 expression, histologic subtype, and performance status. Outcomes will be assessed in accordance with standardized criteria, and all imaging will be reviewed in multidisciplinary tumor boards to ensure consistency.\n\nEthical considerations:\n\nThis is a non-interventional study using retrospective, anonymized data. No additional procedures or patient contact are required. Institutional approvals and data protection regulations will be respected at all participating centers. The study complies with the General Data Protection Regulation (GDPR) and French data privacy laws.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients with metastatic non-small cell lung cancer receiving immunotherapy at the metastatic stage, with no previous immunotherapy treatment.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age \\>18 years\n* Patient with metastatic non-small cell cancer who has received one line of immunotherapy (PEMBROLIZUMAB, ATEZOLIZUMAB and NIVOLUMAB) in stage IV.\n* Disease evaluable according to iRECIST v1.1 criteria\n* For previously irradiated patients, a non-irradiated lesion evaluable according to iRECIST\n* WHO (World Health Organization) score less than or equal to 2.\n\nExclusion Criteria:\n\n* Composite cancer, small cell lung cancer\n* Not metastatic at the time of immunotherapy\n* Has already received one line of immunotherapy for non-small cell lung cancer: antibody against Programmed cell Death protein 1 (anti-PD-1), antibody against Programmed Death-Ligand 1 or 2 (anti-PD-L1 and anti-PD-L2), antiboby against Cluster of Differentiation 137 (anti-CD137), antibody against Cytotoxic T-lymphocyte-antigen-4 (anti-CTLA-4)) .\n* Second active cancer under treatment\n* Immunotherapy for another cancer\n* Withdrawal of consent\n\nNon inclusion Criteria:\n\n\\- Patients treated with DURVALUMAB, on the basis of its marketing authorisation in non-small cell lung cancer and in the adjuvant treatment of NSCLC treated with concomitant radiochemotherapy.'}, 'identificationModule': {'nctId': 'NCT07111104', 'acronym': 'ARIS', 'briefTitle': 'Survival Efficacy of Combined Radiotherapy and Immunotherapy in Patients With Metastatic Non-small Cell Lung Carcinoma', 'organization': {'class': 'OTHER', 'fullName': 'Hopitaux Prives de Metz, Groupe UNEOS'}, 'officialTitle': 'Survival Efficacy of Combined Radiotherapy and Immunotherapy in Patients With Metastatic Non-small Cell Lung Carcinoma: an Observational Retrospective Multicenter Study', 'orgStudyIdInfo': {'id': '2024-001-UNEOS-Obs'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Immunotherapy cohort', 'description': 'This group includes patients with metastatic non small cell lung cancer (NSCLC) who received immune checkpoints inhibitors (Nivolumab, Atezolizumab or Pembrolizumab) without any associated radiotherapy during the course of treatment', 'interventionNames': ['Drug: Immunotherapy']}, {'label': 'Immunotherapy + radiotherapy cohort', 'description': 'This group includes patients with metastatic non-small cell lung cancer (NSCLC) who received immune checkpoint inhibitors (Nivolumab, Atezolizumab, or Pembrolizumab) in combination with radiotherapy. Radiotherapy was delivered either concomitantly or sequentially to immunotherapy.', 'interventionNames': ['Drug: Immunotherapy', 'Radiation: Radiotherapy']}], 'interventions': [{'name': 'Immunotherapy', 'type': 'DRUG', 'otherNames': ['Biological Therapy'], 'description': "The immunotherapy intervention consists of treatment with immune checkpoint inhibitors, specifically Nivolumab (OPDIVO), Atezolizumab (TECENTRIQ), Pembrolizumab (KEYTRUDA).\n\nThese drugs are monoclonal antibodies that block PD-1 or PD-L1 pathways, aiming to enhance the immune system's ability to recognize and destroy cancer cells. The treatment is administered intravenously according to standard dosing schedules.", 'armGroupLabels': ['Immunotherapy + radiotherapy cohort', 'Immunotherapy cohort']}, {'name': 'Radiotherapy', 'type': 'RADIATION', 'otherNames': ['Radiation Therapy', 'External Beam Radiotherapy', 'Radiation Treatment'], 'description': "The radiotherapy intervention involves targeted delivery of ionizing radiation to metastatic lesions. Radiotherapy may be given either concurrently with immunotherapy or sequentially afterward, depending on the patient's treatment plan. The purpose is to achieve local tumor control and potentially enhance the systemic immune response through immunogenic cell death. Different radiation techniques and dose regimens may be employed based on lesion size, location, and clinical considerations.", 'armGroupLabels': ['Immunotherapy + radiotherapy cohort']}]}, 'contactsLocationsModule': {'locations': [{'zip': '57040', 'city': 'Vantoux', 'country': 'France', 'facility': 'Hopitaux Privés de Metz - UNEOS', 'geoPoint': {'lat': 49.12945, 'lon': 6.23201}}], 'overallOfficials': [{'name': 'Ariane Guignard, Resident', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Hopitaux privés de Metz - UNEOS'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hopitaux Prives de Metz, Groupe UNEOS', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}