Ignite Creation Date:
2026-03-26 @ 3:16 PM
Ignite Modification Date:
2026-03-30 @ 7:39 PM
Study NCT ID:
NCT07415668
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-02-17
First Post:
2026-01-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Motor Eloquent Navigated Transcranial Magnetic Stimulation for Radiosurgery Planning
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001932', 'term': 'Brain Neoplasms'}, {'id': 'D009362', 'term': 'Neoplasm Metastasis'}], 'ancestors': [{'id': 'D016543', 'term': 'Central Nervous System Neoplasms'}, {'id': 'D009423', 'term': 'Nervous System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D009385', 'term': 'Neoplastic Processes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-04-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2029-10-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-09', 'studyFirstSubmitDate': '2026-01-29', 'studyFirstSubmitQcDate': '2026-02-09', 'lastUpdatePostDateStruct': {'date': '2026-02-17', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2029-04-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximal radiation dose (Gray)', 'timeFrame': '5 to 2 days before SRS', 'description': 'Maximal radiation dose (Gray) on "functional M1" of each radiotherapy plan (standard and nTMS-adapted); functional M1 is defined by patient specific post-surgical nTMS motor-maps'}], 'secondaryOutcomes': [{'measure': 'Minimal radiation dose on target', 'timeFrame': '5 to 2 days before SRS', 'description': 'Minimal radiation dose on target (resection cavity plus any contrast enhancement with a 2 mm safety margin; Gray)'}, {'measure': 'Motor outcome', 'timeFrame': 'At 3, 6 and 12 month follow-up', 'description': 'Motor outcome (MRCS score) of each patient, at the day of nTMS (as baseline), 3, 6 and 12 months after the first radiation session'}, {'measure': 'Motor outcome', 'timeFrame': 'At 3, 6 and 12 month follow-up', 'description': 'Motor outcome (House and Brackman) of each patient, at the day of nTMS (as baseline), 3, 6 and 12 months after the first radiation session'}, {'measure': 'Motor outcome', 'timeFrame': 'At 3, 6 and 12 month follow-up', 'description': 'Motor outcome (results of pegboard test) of each patient, at the day of nTMS (as baseline), 3, 6 and 12 months after the first radiation session'}, {'measure': 'Motor outcome', 'timeFrame': 'At 3, 6 and 12 month follow-up', 'description': 'Motor outcome (foot tapping test) of each patient, at the day of nTMS (as baseline), 3, 6 and 12 months after the first radiation session'}, {'measure': 'tumor recurrence', 'timeFrame': 'At 3, 6 and 12 month follow-up', 'description': 'recurrence (according to RANO) at 3, 6 and 12 months (yes/no) after first radiation'}, {'measure': 'Quality of life (EQ-5D-5L)', 'timeFrame': 'At 3, 6, and 12 month follow-up', 'description': 'Quality of life via questionnaire (EQ-5D-5L)'}, {'measure': 'Presence of Radiation necrosis', 'timeFrame': 'At 12 month follow-up', 'description': 'Presence of Radiation necrosis in the precentral gyrus after 1 year.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['metastasis', 'Navigated Transcranial Magnetic Stimulation (nTMS)', 'Stereotactic Radiosurgery (SRS)'], 'conditions': ['Metastases to Brain']}, 'referencesModule': {'references': [{'pmid': '32921513', 'type': 'BACKGROUND', 'citation': 'Milano MT, Grimm J, Niemierko A, Soltys SG, Moiseenko V, Redmond KJ, Yorke E, Sahgal A, Xue J, Mahadevan A, Muacevic A, Marks LB, Kleinberg LR. Single- and Multifraction Stereotactic Radiosurgery Dose/Volume Tolerances of the Brain. Int J Radiat Oncol Biol Phys. 2021 May 1;110(1):68-86. doi: 10.1016/j.ijrobp.2020.08.013. Epub 2020 Sep 11.'}, {'pmid': '10487566', 'type': 'BACKGROUND', 'citation': 'Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys. 1999 Sep 1;45(2):427-34. doi: 10.1016/s0360-3016(99)00198-4.'}, {'pmid': '26065612', 'type': 'BACKGROUND', 'citation': 'Lin NU, Lee EQ, Aoyama H, Barani IJ, Barboriak DP, Baumert BG, Bendszus M, Brown PD, Camidge DR, Chang SM, Dancey J, de Vries EG, Gaspar LE, Harris GJ, Hodi FS, Kalkanis SN, Linskey ME, Macdonald DR, Margolin K, Mehta MP, Schiff D, Soffietti R, Suh JH, van den Bent MJ, Vogelbaum MA, Wen PY; Response Assessment in Neuro-Oncology (RANO) group. Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol. 2015 Jun;16(6):e270-8. doi: 10.1016/S1470-2045(15)70057-4. Epub 2015 May 27.'}, {'pmid': '19833552', 'type': 'BACKGROUND', 'citation': 'Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.'}, {'pmid': '30333959', 'type': 'BACKGROUND', 'citation': 'Schwendner MJ, Sollmann N, Diehl CD, Oechsner M, Meyer B, Krieg SM, Combs SE. The Role of Navigated Transcranial Magnetic Stimulation Motor Mapping in Adjuvant Radiotherapy Planning in Patients With Supratentorial Brain Metastases. Front Oncol. 2018 Oct 2;8:424. doi: 10.3389/fonc.2018.00424. eCollection 2018.'}, {'pmid': '8050345', 'type': 'BACKGROUND', 'citation': 'Strnad V, Sauer R. [Prostatic carcinoma]. Dtsch Med Wochenschr. 1994 Jul 29;119(30):1054-6. No abstract available. German.'}, {'pmid': '15871509', 'type': 'BACKGROUND', 'citation': 'Kamada K, Todo T, Masutani Y, Aoki S, Ino K, Takano T, Kirino T, Kawahara N, Morita A. Combined use of tractography-integrated functional neuronavigation and direct fiber stimulation. J Neurosurg. 2005 Apr;102(4):664-72. doi: 10.3171/jns.2005.102.4.0664.'}, {'pmid': '25701297', 'type': 'BACKGROUND', 'citation': "Scoccianti S, Detti B, Gadda D, Greto D, Furfaro I, Meacci F, Simontacchi G, Di Brina L, Bonomo P, Giacomelli I, Meattini I, Mangoni M, Cappelli S, Cassani S, Talamonti C, Bordi L, Livi L. Organs at risk in the brain and their dose-constraints in adults and in children: a radiation oncologist's guide for delineation in everyday practice. Radiother Oncol. 2015 Feb;114(2):230-8. doi: 10.1016/j.radonc.2015.01.016. Epub 2015 Feb 17."}, {'pmid': '22234506', 'type': 'BACKGROUND', 'citation': 'Hodapp N. [The ICRU Report 83: prescribing, recording and reporting photon-beam intensity-modulated radiation therapy (IMRT)]. Strahlenther Onkol. 2012 Jan;188(1):97-9. doi: 10.1007/s00066-011-0015-x. No abstract available. German.'}, {'pmid': '30981901', 'type': 'BACKGROUND', 'citation': 'Seidel K, Hani L, Lutz K, Zbinden C, Redmann A, Consuegra A, Raabe A, Schucht P. Postoperative navigated transcranial magnetic stimulation to predict motor recovery after surgery of tumors in motor eloquent areas. Clin Neurophysiol. 2019 Jun;130(6):952-959. doi: 10.1016/j.clinph.2019.03.015. Epub 2019 Apr 5.'}], 'seeAlsoLinks': [{'url': 'https://www.krebsliga.ch/ueber-krebs/zahlen-fakten', 'label': 'Related Info'}]}, 'descriptionModule': {'briefSummary': 'With this project, the study group wants to investigate whether a postoperative navigated transcranial magnetic stimulation (nTMS) motor map can improve stereotactic radiosurgery (SRS) planning in patients who underwent resection for a brain metastasis near the primary motor cortex. Specifically, the map could allow for more precise location of motor eloquent tissue, thereby minimizing the radiation dose on these areas while preserving high radiation dose on target tissue (i.e. tumor cells).', 'detailedDescription': 'Background:\n\nRadiation therapy is a cornerstone in the management of metastatic brain tumors. It is applied either as a first-line treatment or postoperatively to the resected tumor bed. Delivering a sufficiently high radiation dose to the lesion or tumor bed while preventing neurological deficits due to radionecrosis from overexposure of vulnerable healthy brain tissue remains particularly challenging in eloquent brain regions such as the motor cortex.\n\nAccording to international guidelines (ICRU Reports 50, 62, and 83), target volumes for radiation therapy must be carefully defined, while organs at risk (OARs), including the optic apparatus, cochlea, hippocampus, brainstem, and pituitary gland, must be spared. The motor cortex (M1) and corticospinal tract (CST) should likewise be preserved; however, they are not formally defined as OARs in current guidelines, and their precise delineation is technically demanding.\n\nThe anatomical precentral gyrus ("anatomical M1") does not exactly correspond to the functional location of motor control ("functional M1"). Conventional imaging techniques such as functional MRI (fMRI) and diffusion tensor imaging (DTI) provide limited spatial accuracy, with localization errors of up to 1 cm. In contrast, navigated transcranial magnetic stimulation (nTMS) is a noninvasive method that identifies motor-eloquent regions based on individual MRI data, offering more accurate functional mapping for radiation treatment planning. This raises the question of whether integrating postoperative, pre-radiotherapy nTMS maps could enable more tailored and precise radiation therapy plans.\n\nPrevious studies have shown that nTMS demonstrates a median deviation of only 5.2 mm compared with direct cortical stimulation (the gold standard), whereas fMRI may deviate even more than 1 cm. Especially in patients with tumors involving the motor cortex, nTMS has been shown to provide superior spatial accuracy. Preliminary data further suggest that incorporating nTMS into radiotherapy planning may reduce radiation exposure to the motor cortex and CST while maintaining optimal target coverage.\n\nHowever, published studies so far have relied exclusively on preoperative imaging. Postoperative anatomical changes, due to brain shift and variations in the resection cavity, can render these maps inaccurate for postoperative planning. It therefore remains to be determined whether updating nTMS maps using postoperative MRI obtained immediately before radiotherapy can enhance treatment precision and clinical outcomes.\n\nObjective:\n\nThe objective of this study is to address the following questions in patients with resected brain metastases involving or adjacent to the motor cortex:\n\n1. Is it possible to simultaneously maintain the sufficient radiation dose in the region of the lesion and keep the dose on the functional primary motor area (M1) as low as possible?\n2. Does the integration of nTMS mapping into radio-oncological treatment planning and the associated dose reduction to M1 affect clinical outcomes?\n3. Is there a correlation between the final dose received by the functional M1 and the clinical/oncological outcome (post-radiosurgery motor function, radionecrosis and local tumor control at 3, 6- and 12-months follow-up)?\n\nMethods:\n\nThe planning of SRS will be performed by a team of radiation oncologists at the Inselspital, Bern University Hospital with extensive experience in brain metastases treatment. Manual segmentations of the target volume and nTMS points will be performed. The included cases will be reviewed for the extent/dose of the treatment plan and two treatment plans will be created: a "standard" and an "nTMS-adapted" treatment plan.\n\nFor the "nTMS-adapted" plan, the nTMS motor map will be fused with the planning MRI. The motor map of each patient (regions of interest defined by the positive MEP responses) will be used to define "functional M1". The treatment dose will be prescribed to the planning target volume (Planning target volume (PTV): resection cavity plus any contrast enhancement with a 2 mm safety margin in patients with surgery). This plan will be optimized according to nTMS motor maps by reducing the dose applied to the motor eloquent tissue as low as reasonably possible by constraining the dose prescription in this area to 15 Gy in single fraction. PTV overlap with the motor maps will not be spared. The radiation oncologist selects the nTMS-adapted plan if it covers at least 95% of the target volume; otherwise, the standard plan is chosen to ensure adequate dose coverage.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Informed consent\n2. Age ≥ 18 years\n3. Cerebral metastasis within or adjacent to the primary motor cortex (≤10 mm)\n4. Resection of tumor\n5. Eligible for and planned to undergo postresection radiosurgery at Inselspital Bern\n\nExclusion Criteria:\n\n1. Contraindication to TMS (e.g. Cochlear Implant, other metallic or electrical implants, excluding teeth and post craniotomy, Meniere's disease, pacemaker, deep brain stimulation electrodes, refractory convulsion, symptomatic tinnitus, depression diagnosed by a specialist, psychosis)\n2. Prior cerebral radiation therapy within the affected precentral gyrus/affecting the planned SRS plan\n3. Planned whole brain radiotherapy\n4. Second lesion within 2 cm ipsilateral in the primary motor cortex\n5. Infection or difficulties in wound healing within the last two weeks prior inclusion\n6. Pregnancy"}, 'identificationModule': {'nctId': 'NCT07415668', 'acronym': 'MENTOR', 'briefTitle': 'Motor Eloquent Navigated Transcranial Magnetic Stimulation for Radiosurgery Planning', 'organization': {'class': 'OTHER', 'fullName': 'Insel Gruppe AG, University Hospital Bern'}, 'officialTitle': 'Motor Eloquent Navigated Transcranial Magnetic Stimulation for Radiosurgery Planning', 'orgStudyIdInfo': {'id': 'MENTOR'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'MENTOR', 'description': 'Every patient will undergo a postoperative nTMS motor mapping, and both the "standard" and "nTMS-adapted" SRS plan will be created for every patient. The plan will be selected by the radiation oncologist, depending on whether at least 95% of the dose is administered to the target volume with the "nTMS-adapted" plan or not. Every patient then receives SRS.', 'interventionNames': ['Device: Navigated Transcranial Magnetic Stimulation (nTMS)']}], 'interventions': [{'name': 'Navigated Transcranial Magnetic Stimulation (nTMS)', 'type': 'DEVICE', 'description': 'Every patient will undergo a postoperative nTMS motor mapping, and both the "standard" and "nTMS-adapted" SRS plan will be created for every patient. The plan will be selected by the radiation oncologist, depending on whether at least 95% of the dose is administered to the target volume with the "nTMS-adapted" plan or not. Every patient then receives SRS.', 'armGroupLabels': ['MENTOR']}]}, 'contactsLocationsModule': {'locations': [{'zip': '3010', 'city': 'Bern', 'country': 'Switzerland', 'contacts': [{'name': 'Kathleen Seidel, MD', 'role': 'CONTACT', 'email': 'kathleen.seidel@insel.ch', 'phone': '+41316322409'}, {'name': 'Katharina Lutz, MD', 'role': 'CONTACT', 'email': 'katharina.lutz@insel.ch', 'phone': '+41316322409'}], 'facility': 'University Hostpital Bern, Department of Neurosurgery Bern', 'geoPoint': {'lat': 46.94809, 'lon': 7.44744}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Insel Gruppe AG, University Hospital Bern', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}