Ignite Creation Date:
2025-12-25 @ 3:37 AM
Ignite Modification Date:
2026-02-01 @ 10:28 PM
Study NCT ID:
NCT02685605
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-10-14
First Post:
2016-02-05
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Peru']}, 'conditionBrowseModule': {'meshes': [{'id': 'D005909', 'term': 'Glioblastoma'}], 'ancestors': [{'id': 'D001254', 'term': 'Astrocytoma'}, {'id': 'D005910', 'term': 'Glioma'}, {'id': 'D018302', 'term': 'Neoplasms, Neuroepithelial'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D059248', 'term': 'Chemoradiotherapy'}, {'id': 'D000077204', 'term': 'Temozolomide'}], 'ancestors': [{'id': 'D003131', 'term': 'Combined Modality Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D004358', 'term': 'Drug Therapy'}, {'id': 'D011878', 'term': 'Radiotherapy'}, {'id': 'D003606', 'term': 'Dacarbazine'}, {'id': 'D014226', 'term': 'Triazenes'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 314}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2016-12-09', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-10', 'completionDateStruct': {'date': '2026-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-10-10', 'studyFirstSubmitDate': '2016-02-05', 'studyFirstSubmitQcDate': '2016-02-14', 'lastUpdatePostDateStruct': {'date': '2025-10-14', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2016-02-19', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2025-11', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Median Progression-Free Survival', 'timeFrame': '24 Months', 'description': 'Determined according to modified Response Assessment in Neuro-Oncology (RANO) criteria and serial perfusion imaging'}], 'secondaryOutcomes': [{'measure': 'Median Overall Survival', 'timeFrame': '24 Months'}, {'measure': 'PFS within a 1-2 cm margin around the cavity', 'timeFrame': '24 Months', 'description': 'Determined by serial contrast-enhanced MRI scans using modified RANO criteria and serial perfusion imaging'}, {'measure': 'OS with respect to Age', 'timeFrame': '24 Months', 'description': 'Median overall survival of patients \\<65 vs. ≥ 65 years'}, {'measure': 'PFS with respect to Age', 'timeFrame': '24 Months', 'description': 'Progression-free survival of patients \\<65 vs. ≥ 65 years; determined according to modified RANO criteria and serial perfusion imaging'}, {'measure': 'OS with respect to KPS', 'timeFrame': '24 Months', 'description': 'Median overall survival of patients with KPS 80-100% vs. 60-70%'}, {'measure': 'PFS with respect to KPS', 'timeFrame': '24 Months', 'description': 'Progression-free survival of patients with KPS 80-100% vs. 60-70%; determined according to modified RANO criteria and serial perfusion imaging'}, {'measure': 'OS with respect to thickness of anticipated T1-Gd-enhancing (remaining) tumor margin', 'timeFrame': '24 Months', 'description': 'Thickness of anticipated T1-Gd-enhancing (remaining) tumor margin as per the discretion of the surgeon (margin ≥0.5 cm or multiple spots of residual tumor within the cavity vs. \\<0.5 cm)'}, {'measure': 'PFS with respect to thickness of anticipated T1-Gd-enhancing (remaining) tumor margin', 'timeFrame': '24 Months', 'description': 'Thickness of anticipated T1-Gd-enhancing (remaining) tumor margin as per the discretion of the surgeon (margin ≥0.5 cm or multiple spots of residual tumor within the cavity vs. \\<0.5 cm); determined according to modified RANO criteria and serial perfusion imaging'}, {'measure': 'OS with respect to extent of resection', 'timeFrame': '24 Months', 'description': 'Early postoperative MRI scans must be used to determine the extent of resection (EoR). The EoR is given as sum of all maximum diameters of residual lesions in cm. OS will be calculated for the following groups:\n\n* Max Diameter group 0: 0 cm (no residual tumor)\n* Max Diameter group 1: \\>0 to ≤1.5 cm (cumulative if multiple residual lesions)\n* Max Diameter group 2: \\>1.5 cm (cumulative if multiple residual lesions)'}, {'measure': 'PFS with respect to extent of resection', 'timeFrame': '24 Months', 'description': 'Early postoperative MRI scans must be used to determine the extent of resection (EoR). The EoR is given as sum of all maximum diameters of residual lesions in cm. PFS will be determined according to modified RANO criteria and serial perfusion imaging for the following groups:\n\n* Max Diameter group 0: 0 cm (no residual tumor)\n* Max Diameter group 1: \\>0 to ≤1.5 cm (cumulative if multiple residual lesions)\n* Max Diameter group 2: \\>1.5 cm (cumulative if multiple residual lesions)'}, {'measure': 'OS with respect to MGMT promoter methylation status', 'timeFrame': '24 Months', 'description': 'OS in patients with promoter methylation vs. no promoter methylation'}, {'measure': 'PFS with respect to MGMT promoter methylation status', 'timeFrame': '24 Months', 'description': 'PFS in patients with promoter methylation vs. no promoter methylation; determined according to modified RANO criteria and serial perfusion imaging'}, {'measure': 'Quality of Life (QoL) questionnaire', 'timeFrame': '24 Months', 'description': 'Assessed by European Organization for Research and Treatment (EORTC)- Quality of Life Questionnaires (QLQ C30/BN20)'}, {'measure': 'Activities of daily living (ADL), assessed using the Barthel Index (Mahoney & Barthel, 1965).', 'timeFrame': '24 Months', 'description': 'Change in functional outcomes as measured by BI from its baseline value.'}, {'measure': 'Radiation-related (acute / early delayed / late) neurotoxicity', 'timeFrame': '24 Months', 'description': 'Assessed by regular neurological examinations and serial MRI scans'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Glioblastoma', 'Intraoperative Radiotherapy', 'Radiotherapy Dose Escalation'], 'conditions': ['Glioblastoma']}, 'referencesModule': {'references': [{'pmid': '25535398', 'type': 'BACKGROUND', 'citation': 'Giordano FA, Brehmer S, Abo-Madyan Y, Welzel G, Sperk E, Keller A, Schneider F, Clausen S, Herskind C, Schmiedek P, Wenz F. INTRAGO: intraoperative radiotherapy in glioblastoma multiforme-a phase I/II dose escalation study. BMC Cancer. 2014 Dec 22;14:992. doi: 10.1186/1471-2407-14-992.'}, {'pmid': '31629553', 'type': 'BACKGROUND', 'citation': 'Sarria GR, Sperk E, Han X, Sarria GJ, Wenz F, Brehmer S, Fu B, Min S, Zhang H, Qin S, Qiu X, Hanggi D, Abo-Madyan Y, Martinez D, Cabrera C, Giordano FA. Intraoperative radiotherapy for glioblastoma: an international pooled analysis. Radiother Oncol. 2020 Jan;142:162-167. doi: 10.1016/j.radonc.2019.09.023. Epub 2019 Oct 16.'}, {'pmid': '37150259', 'type': 'BACKGROUND', 'citation': 'Ayala Alvarez DS, Watson PGF, Popovic M, Heng VJ, Evans MDC, Panet-Raymond V, Seuntjens J. Evaluation of Dosimetry Formalisms in Intraoperative Radiation Therapy of Glioblastoma. Int J Radiat Oncol Biol Phys. 2023 Nov 1;117(3):763-773. doi: 10.1016/j.ijrobp.2023.04.031. Epub 2023 May 5.'}, {'pmid': '34858846', 'type': 'BACKGROUND', 'citation': 'Cifarelli CP, Jacobson GM. Intraoperative Radiotherapy in Brain Malignancies: Indications and Outcomes in Primary and Metastatic Brain Tumors. Front Oncol. 2021 Nov 11;11:768168. doi: 10.3389/fonc.2021.768168. eCollection 2021.'}, {'pmid': '34778080', 'type': 'BACKGROUND', 'citation': 'Sarria GR, Smalec Z, Muedder T, Holz JA, Scafa D, Koch D, Garbe S, Schneider M, Hamed M, Vatter H, Herrlinger U, Giordano FA, Schmeel LC. Dosimetric Comparison of Upfront Boosting With Stereotactic Radiosurgery Versus Intraoperative Radiotherapy for Glioblastoma. Front Oncol. 2021 Oct 28;11:759873. doi: 10.3389/fonc.2021.759873. eCollection 2021.'}, {'pmid': '29528443', 'type': 'DERIVED', 'citation': 'Giordano FA, Brehmer S, Murle B, Welzel G, Sperk E, Keller A, Abo-Madyan Y, Scherzinger E, Clausen S, Schneider F, Herskind C, Glas M, Seiz-Rosenhagen M, Groden C, Hanggi D, Schmiedek P, Emami B, Souhami L, Petrecca K, Wenz F. Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO): An Open-Label, Dose-Escalation Phase I/II Trial. Neurosurgery. 2019 Jan 1;84(1):41-49. doi: 10.1093/neuros/nyy018.'}]}, 'descriptionModule': {'briefSummary': 'INTRAGO II resembles a multicentric, prospective, randomized, 2-arm, open-label clinical phase III trial which tests if the median progression-free survival (PFS) of patients with newly diagnosed glioblastoma multiforme (GBM) can be improved by the addition of intraoperative radiotherapy (IORT) to standard radiochemotherapy.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria\n\n1. Age ≥18 and ≤ 80 years\n2. Karnofsky Performance Score (KPS) ≥ 60%\n3. Supratentorial T1-Gd enhancing lesion(s) amenable to total resection\n4. Legal capacity and ability of subject to understand character and individual consequences of the clinical trial\n5. Patient's written IC obtained at least 24h prior to surgery\n6. For women with childbearing potential: adequate contraception\n7. Patients must have adequate organ functions\n\n Bone marrow function:\n * Platelets ≥ 75.000/μL\n * WBC ≥ 3.000/μL\n * Hemoglobin ≥ 10.0 g/dL\n\n Liver Function:\n * ASAT and ALAT ≤ 3.0 times ULN\n * ALP ≤ 2.5 times ULN\n * Total Serum Bilirubin \\< 1.5 times ULN\n\n Renal Function:\n * Serum Creatinine ≤ 1.5 times ULN\n\n Inclusion Criteria Related to Surgery:\n8. IORT must be technically feasible\n9. Histology supports diagnosis of GBM\n\nExclusion Criteria\n\n1. Multicentric disease (e.g. in both hemispheres) or non-resectable satellite lesions\n2. Previous cranial radiation therapy\n3. Cytostatic therapy / chemotherapy for cancer within the past 5 years\n4. History of cancers or other comorbidities that limit life expectancy to less than five years\n5. Previous therapy with anti-angiogenic substances (such as bevacizumab)\n6. Technical impossibility to use MRI or known allergies against MRI and/or CT contrast agents\n7. Participation in other clinical trials testing cancer-derived investigational agents/procedures.\n8. Pregnant or breast feeding patients\n9. Fertile patients refusing to use safe contraceptive methods during the study\n\n Exclusion Criteria Related to Surgery:\n10. Active egress of fluids from a ventricular defect\n11. In-field risk organs and/or IORT dose \\>8 Gy to any risk organ"}, 'identificationModule': {'nctId': 'NCT02685605', 'acronym': 'INTRAGO-II', 'briefTitle': 'Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme', 'organization': {'class': 'OTHER', 'fullName': 'Universitätsmedizin Mannheim'}, 'officialTitle': 'A Multicenter Randomized Phase III Trial on INTraoperative RAdiotherapy in Newly Diagnosed GliOblastoma Multiforme (INTRAGO II)', 'orgStudyIdInfo': {'id': 'INTRAGO-II'}, 'secondaryIdInfos': [{'id': 'ARO-2016-1', 'type': 'OTHER', 'domain': 'Working Party for Radiation Oncology (ARO) of the DKG'}, {'id': 'AG-NRO-03', 'type': 'OTHER', 'domain': 'German Society for Radiation Oncology (DEGRO)'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Experimental Arm (A)', 'description': 'Standard surgery plus intraoperative radiotherapy (20-30 Gy) followed by radiochemotherapy (EBRT: 60 Gy, 75 mg/m2/d temozolomide) and adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).', 'interventionNames': ['Procedure: Standard surgery', 'Radiation: Intraoperative radiotherapy', 'Radiation: Radiochemotherapy', 'Drug: Temozolomide']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Control Arm (B)', 'description': 'Standard surgery followed by radiochemotherapy (EBRT: 60 Gy, 75 mg/m2/d temozolomide) and adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).', 'interventionNames': ['Procedure: Standard surgery', 'Radiation: Radiochemotherapy', 'Drug: Temozolomide']}], 'interventions': [{'name': 'Standard surgery', 'type': 'PROCEDURE', 'armGroupLabels': ['Control Arm (B)', 'Experimental Arm (A)']}, {'name': 'Intraoperative radiotherapy', 'type': 'RADIATION', 'otherNames': ['IORT'], 'description': 'Dose to applicator surface: 20-30 Gy; Carl Zeiss INTRABEAM System. IORT with a surface dose of 30 Gy is recommended.Should the proximity to any risk structure not allow to apply 30 Gy, a dose reduction by up to 10 Gy (resulting in a surface dose of 20 Gy) is allowed.', 'armGroupLabels': ['Experimental Arm (A)']}, {'name': 'Radiochemotherapy', 'type': 'RADIATION', 'description': 'EBRT to 60 Gy plus 75 mg/m2/d temozolomide', 'armGroupLabels': ['Control Arm (B)', 'Experimental Arm (A)']}, {'name': 'Temozolomide', 'type': 'DRUG', 'description': 'Adjuvant chemotherapy with 150-200 mg/m2/d temozolomide per cycle (5/28 days).', 'armGroupLabels': ['Control Arm (B)', 'Experimental Arm (A)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '85013', 'city': 'Phoenix', 'state': 'Arizona', 'country': 'United States', 'facility': 'Barrow Neurological Institute (SJHMC)', 'geoPoint': {'lat': 33.44838, 'lon': -112.07404}}, {'zip': '60153', 'city': 'Maywood', 'state': 'Illinois', 'country': 'United States', 'facility': 'Stritch School of Medicine Loyola University', 'geoPoint': {'lat': 41.8792, 'lon': -87.84312}}, {'zip': '11042', 'city': 'Lake Success', 'state': 'New York', 'country': 'United States', 'facility': 'Long Island Jewish Medical Center, North Shore University Hospital', 'geoPoint': {'lat': 40.77066, 'lon': -73.71763}}, {'zip': '10028', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Lenox Hill Hospital, Hofstra Northwell School of Medicine', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '26506-9260', 'city': 'Morgantown', 'state': 'West Virginia', 'country': 'United States', 'facility': 'West Virginia University', 'geoPoint': {'lat': 39.62953, 'lon': -79.9559}}, {'zip': '01323-020', 'city': 'São Paulo', 'country': 'Brazil', 'facility': 'Hospital Alemão Oswaldo Cruz', 'geoPoint': {'lat': -23.5475, 'lon': -46.63611}}, {'zip': 'H3A 2B4', 'city': 'Montreal', 'state': 'Quebec', 'country': 'Canada', 'facility': 'Montreal Neurological Institute and Hospital', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}, {'zip': '100050', 'city': 'Beijing', 'country': 'China', 'facility': 'Beijing Tian Tan Hospital, Capital Medical University', 'geoPoint': {'lat': 39.9075, 'lon': 116.39723}}, {'zip': '86156', 'city': 'Augsburg', 'country': 'Germany', 'facility': 'University Hospital Augsburg', 'geoPoint': {'lat': 48.37154, 'lon': 10.89851}}, {'zip': '13353', 'city': 'Berlin', 'country': 'Germany', 'facility': 'Charité - Universitätsmedizin', 'geoPoint': {'lat': 52.52437, 'lon': 13.41053}}, {'city': 'Leipzig', 'country': 'Germany', 'facility': 'St. Georg Hospital', 'geoPoint': {'lat': 51.33962, 'lon': 12.37129}}, {'zip': '68167', 'city': 'Mannheim', 'country': 'Germany', 'facility': 'University Hospital Mannheim', 'geoPoint': {'lat': 49.4891, 'lon': 8.46694}}, {'zip': '81675', 'city': 'Munich', 'country': 'Germany', 'facility': 'Technical University of Munich (TUM), Department of Radiation Oncology', 'geoPoint': {'lat': 48.13743, 'lon': 11.57549}}, {'zip': '70174', 'city': 'Stuttgart', 'country': 'Germany', 'facility': 'Klinikum Stuttgart', 'geoPoint': {'lat': 48.78232, 'lon': 9.17702}}, {'zip': '42283', 'city': 'Wuppertal', 'country': 'Germany', 'facility': 'Helios University Hospital Wuppertal', 'geoPoint': {'lat': 51.25627, 'lon': 7.14816}}, {'zip': '06273', 'city': 'Seoul', 'country': 'South Korea', 'facility': 'Gangnam Severance Hospital, Yonsei University College of Medicine', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}, {'zip': '08908', 'city': 'Barcelona', 'country': 'Spain', 'facility': 'Catalan Institute of Oncology (ICO)', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'city': 'Córdoba', 'country': 'Spain', 'facility': 'Hospital Reina Sofia', 'geoPoint': {'lat': 37.89155, 'lon': -4.77275}}, {'zip': 'W1G 6BW', 'city': 'London', 'country': 'United Kingdom', 'facility': 'The London Clinic', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'overallOfficials': [{'name': 'Frank A. Giordano, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Germany'}, {'name': 'Kevin Petrecca, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Department of Neurosurgery, Montréal Neurological, Institute and Hospital, Montréal, Canada'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Universitätsmedizin Mannheim', 'class': 'OTHER'}, 'collaborators': [{'name': 'Carl Zeiss Meditec AG', 'class': 'INDUSTRY'}, {'name': 'University of California, Los Angeles', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'PI (Chair)', 'investigatorFullName': 'Frank A. Giordano', 'investigatorAffiliation': 'Heidelberg University'}}}}