Ignite Creation Date:
2025-12-25 @ 12:21 AM
Ignite Modification Date:
2026-01-10 @ 8:28 PM
Study NCT ID:
NCT05317858
Status:
RECRUITING
Last Update Posted:
2025-12-10
First Post:
2022-03-01
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Blood-brain Barrier (BBB) Opening Using Exablate Focused Ultrasound With Standard of Care Treatment of NSCLC Brain Mets
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001932', 'term': 'Brain Neoplasms'}, {'id': 'D002289', 'term': 'Carcinoma, Non-Small-Cell Lung'}], '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': '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': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C582435', 'term': 'pembrolizumab'}, {'id': 'C000594389', 'term': 'atezolizumab'}, {'id': 'C000627974', 'term': 'cemiplimab'}, {'id': 'D000077594', 'term': 'Nivolumab'}], 'ancestors': [{'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR'], 'maskingDescription': 'Imaging Core Lab is Blinded'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2022-08-12', 'type': 'ACTUAL'}, 'statusVerifiedDate': '2025-12', 'completionDateStruct': {'date': '2027-12-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-12-03', 'studyFirstSubmitDate': '2022-03-01', 'studyFirstSubmitQcDate': '2022-03-31', 'lastUpdatePostDateStruct': {'date': '2025-12-10', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2022-04-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-06-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Patient reported quality of life measurement questionnaires', 'timeFrame': 'up to 6 months', 'description': 'patient reported health and quality of life questionnaire completed every 3 weeks up to 6 months during treatment cycle.'}, {'measure': 'Measurement of BBB Opening', 'timeFrame': 'up to 6 months', 'description': 'Measurement of blood brain barrier opening (BBBO) assessment of post-sonication contrast-enhanced MR imaging evaluated every 3 weeks up to 6 months in comparison with pre-sonication imaging.'}], 'primaryOutcomes': [{'measure': 'Adverse events', 'timeFrame': 'up to 6 months', 'description': 'Adverse events \\[ Time Frame: Through study completion, up to 6 months\\]. All adverse events and/or Serious Adverse Events will be documented and reported according to CTCAE criteria.'}, {'measure': 'tumor lesion(s) on the MRI images', 'timeFrame': 'up to 6 months', 'description': 'Efficacy will be determined by the response of the tumor lesion(s) compared to baseline. Tumor lesions on the MRI images (units: mm) will be measured every three weeks up to six months.'}], 'secondaryOutcomes': [{'measure': 'evaluation of Neuro Oncology Brain Mets (RANO-BM) response', 'timeFrame': 'up to 6 months', 'description': 'The evaluation of the percentages of subjects that achieved the stable disease (SD), partial response (PR) as the best objective response using the response assessment in Neuro Oncology Brain Mets (RANO-BM) response criteria measured at baseline and every 3 weeks during each treatment cycle to up to 6 months of therapy.'}, {'measure': 'Time to response for brain metastases by treatment arm [applicable to the completed stage 1a only]', 'timeFrame': 'up to 6 months', 'description': 'The time to achieve a confirmed complete response or partial response for brain metastases by treatment arm as assessed using the RANO-BM criteria evaluated every 3 weeks up to 6 months during treatment cycles.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isUnapprovedDevice': True, 'isFdaRegulatedDevice': True}, 'conditionsModule': {'conditions': ['Brain Tumor', 'Non Small Cell Lung Cancer']}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier opening with Exablate Model 4000 Type 2.0/2.1 for the treatment of NSCLC brain metastases in patients who are undergoing planned FDA approved, on-label systemic therapy utilizing immune checkpoint inhibitors.', 'detailedDescription': 'This is a prospective, multi-center, randomized, two-arm, controlled, pivotal clinical trial to evaluate the safety and efficacy of targeted blood brain barrier opening using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned FDA approved, on-label systemic therapy utilizing immune checkpoint inhibitors for their primary disease. The study will be conducted at up to 30 centers in the US. The immunotherapy regimen (every 3 weeks for 6 cycles) of prescribed ICI therapy is per the FDA approved labeling and the subjects prescribed standard of care therapy for their primary NSCLC. The study aims to demonstrate superiority of Exablate BBBO targeted to their brain metastases over the standard of care without Exablate BBBO with respect to the percentage of subjects achieving Objective Response Rate (ORR) by 6 months follow-up.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '100 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Participant is ≥ 18 years of age\n* The participant provides written informed consent for the trial\n* Participant is willing to comply with all study procedures for the duration of the study\n* Participant has a Karnofsky Performance Status ≥ 70% and/or ECOG 0-2\n* Participant is a NSCLC subject prescribed immune checkpoint inhibitor systemic therapy according to on-label use with the target brain lesion(s) measuring ≥ 0.5 cm in longest diameter. Target mets may include: De novo mets for which surgery and radiation can be deferred, Mets with or without history of prior radiation, Mets with history of radiation after at least 8 weeks since last radiation treatment, and In the event a previously treated met has progressed according to institutional practice within 4 weeks post radiation treatment, the met may be study eligible, and/or if in the opinion of the Investigator, the subject may benefit from the study procedure.\n* Female subject is not planning pregnancy during the study duration and confirmed NOT PREGNANT each procedure day.\n* Screening/Baseline laboratory values Screening/Baseline should adhere to local standard of care lab values for ICI therapy\n\nExclusion Criteria\n\n* Participant has evidence of acute intracranial hemorrhage\n* Participant at risk for spontaneous intracranial hemorrhage (e.g., history of metastatic melanoma or other tissue histology).\n* Participant has signs and symptoms of increased intracranial pressure or symptomatic mass effect, midline shift or evidence of subfalcine, uncal or tonsillar herniation.\n* Participant receiving Bevacizumab (Avastin) therapy, or other drugs with a proclivity for causing bleeding.\n* History of bleeding disorders or tissue pathologies which increase the subject's risk of hemorrhage for anticoagulation medications, implement pre-surgical standard procedure to avoid increased risk of a bleeding event.\n* Participant has an infectious viral infection such as active Hepatitis B, Hepatitis C or detectable HIV viral load or participants with active bacterial infection such as TB (Bacillus tuberculosis) that may, in the opinion of the investigator, interfere with the subject receiving the study therapy or procedures or otherwise impact their participation in the trial.\n* Subjects with evidence of cranial or systemic infection.\n* Participant has received a solid organ or hematopoietic stem cell transplant.\n* Participant has received a live vaccine within 28 days prior to the first on-study ICI infusion with or without Exablate.\n* Known sensitivity to DEFINITY® ultrasound contrast agent or hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol, as found in MiraLAX and bowel prep products.\n* Contraindications to MRI and gadolinium-DTPA including non-MRI-compatible implanted devices, severe claustrophobia, unable to lie supine in MRI.\n* Subjects with significant liver dysfunction, (cirrhosis, hemochromatosis, severe alcohol abuse, or active hepatitis (autoimmune or infectious))\n* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first on-study ICI infusion with or without Exablate. Note: prophylactic steroid use for ICI and chemotherapy infusion per institutional practice is allowed per protocol.\n* Has a known additional malignancy that requires active treatment that would interfere with study procedures.\n* Known presence of leptomeningeal disease.\n* Has a diagnosis of active autoimmune disease (e.g., autoimmune Hepatitis, Guillain-Barre Syndrome, etc.) requiring systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. History of (non-infectious) pneumonitis that requires steroids or has current pneumonitis\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.\n* Subject is currently enrolled in another intervention based clinical trial"}, 'identificationModule': {'nctId': 'NCT05317858', 'acronym': 'LIMITLESS', 'briefTitle': 'Blood-brain Barrier (BBB) Opening Using Exablate Focused Ultrasound With Standard of Care Treatment of NSCLC Brain Mets', 'organization': {'class': 'INDUSTRY', 'fullName': 'InSightec'}, 'officialTitle': 'A Randomized Pivotal Study Assessing the Safety and Efficacy of Targeted Blood-brain Barrier (BBB) Opening Using Exablate Focused Ultrasound During the Standard of Care Treatment of Brain Metastases of Non-small Cell Lung Cancer (NSCLC) Origin', 'orgStudyIdInfo': {'id': 'BT012'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'ICI Systemic Therapy with Exablate BBBO', 'description': 'Using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned ICI Systemic Therapy.', 'interventionNames': ['Device: Blood Brain Barrier Opening - Oncology', 'Drug: Pembrolizumab', 'Drug: Atezolizumab', 'Drug: Cemiplimab', 'Drug: Nivolumab', 'Drug: Iptilimumab']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Control Arm (ICI Systemic Therapy on-label use only)', 'description': 'subjects will undergo planned on-label ICI Systemic Therapy.', 'interventionNames': ['Drug: Pembrolizumab', 'Drug: Atezolizumab', 'Drug: Cemiplimab', 'Drug: Nivolumab', 'Drug: Iptilimumab']}], 'interventions': [{'name': 'Blood Brain Barrier Opening - Oncology', 'type': 'DEVICE', 'otherNames': ['Exablate BBBO'], 'description': 'BBB opening via Exablate Type 2 system with microbubble resonators on the day of ICI infusion to treat brain metastases.', 'armGroupLabels': ['ICI Systemic Therapy with Exablate BBBO']}, {'name': 'Pembrolizumab', 'type': 'DRUG', 'otherNames': ['KEYTRUDA'], 'description': 'Pembrolizumab infusion', 'armGroupLabels': ['Control Arm (ICI Systemic Therapy on-label use only)', 'ICI Systemic Therapy with Exablate BBBO']}, {'name': 'Atezolizumab', 'type': 'DRUG', 'otherNames': ['Tecentriq'], 'description': 'Atezolizumab infusion', 'armGroupLabels': ['Control Arm (ICI Systemic Therapy on-label use only)', 'ICI Systemic Therapy with Exablate BBBO']}, {'name': 'Cemiplimab', 'type': 'DRUG', 'otherNames': ['LIBTAYO'], 'description': 'Cemiplimab infusion', 'armGroupLabels': ['Control Arm (ICI Systemic Therapy on-label use only)', 'ICI Systemic Therapy with Exablate BBBO']}, {'name': 'Nivolumab', 'type': 'DRUG', 'description': 'Nivolumab infusion', 'armGroupLabels': ['Control Arm (ICI Systemic Therapy on-label use only)', 'ICI Systemic Therapy with Exablate BBBO']}, {'name': 'Iptilimumab', 'type': 'DRUG', 'description': 'Iptilimumab infusion', 'armGroupLabels': ['Control Arm (ICI Systemic Therapy on-label use only)', 'ICI Systemic Therapy with Exablate BBBO']}]}, 'contactsLocationsModule': {'locations': [{'zip': '85013', 'city': 'Phoenix', 'state': 'Arizona', 'status': 'NOT_YET_RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Jamie Sanders', 'role': 'CONTACT', 'email': 'research@ivybraintumorcenter.org', 'phone': '602-406-8605'}, {'name': 'Nader Sanai, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': "St. Joseph's Hospital and Medical Center", 'geoPoint': {'lat': 33.44838, 'lon': -112.07404}}, {'zip': '33176', 'city': 'Miami', 'state': 'Florida', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Daylan L Santana, RN', 'role': 'CONTACT', 'email': 'DaylenS@baptisthealth.net', 'phone': '7865278528'}, {'name': 'Juliana Montoya', 'role': 'CONTACT', 'email': 'Juliana.Montoya@BaptistHealth.ne', 'phone': '786-527-8864'}, {'name': 'Manmeet S Ahluwalia, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Miami Cancer Institute at Baptist Health', 'geoPoint': {'lat': 25.77427, 'lon': -80.19366}}, {'zip': '33612', 'city': 'Tampa', 'state': 'Florida', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Sebastian Matzza', 'role': 'CONTACT', 'email': 'Sebastian.Matzza@moffitt.org', 'phone': '813-745-1158'}, {'name': 'Carie Bliss', 'role': 'CONTACT', 'email': 'Carie.Bliss@moffitt.org', 'phone': '(813) 745-2131'}, {'name': 'Yolanda Pina, Neuro-Oncology', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Moffitt Cancer Center', 'geoPoint': {'lat': 27.94752, 'lon': -82.45843}}, {'zip': '21201', 'city': 'Baltimore', 'state': 'Maryland', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Kaitlyn Henry', 'role': 'CONTACT', 'email': 'KHenry@som.umaryland.edu', 'phone': '410-328-0939'}, {'name': 'Rayne Noyes', 'role': 'CONTACT', 'email': 'anoyes@som.umaryland.edu', 'phone': '410-328-5332'}, {'name': 'Graeme Woodworth, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Howard Eisenberg, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Alexander Ksendzovsky, MD', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'University of Maryland', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '02903', 'city': 'Providence', 'state': 'Rhode Island', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Maria Duffy', 'role': 'CONTACT', 'email': 'mduffy@brownhealth.org', 'phone': '(401) 444-2243'}, {'name': 'Owen Leary', 'role': 'CONTACT', 'email': 'owen.leary@brownhealth.org', 'phone': '(401) 606-8388'}, {'name': 'Clark Chen', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Rhode Island Hospital', 'geoPoint': {'lat': 41.82399, 'lon': -71.41283}}, {'zip': '23235', 'city': 'Richmond', 'state': 'Virginia', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Kanwalcharan S Sahni, MD', 'role': 'CONTACT', 'email': 'ksinghsahni@gmail.com', 'phone': '804-330-4990'}, {'name': 'Kanwalcharan Sahni, Neurosurgery', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Johnston Willis Hospital', 'geoPoint': {'lat': 37.55376, 'lon': -77.46026}}, {'zip': 'M4N 3M5', 'city': 'Toronto', 'state': 'Ontario', 'status': 'COMPLETED', 'country': 'Canada', 'facility': 'Sunnybrook Research Institute', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': '06351', 'city': 'Seoul', 'state': 'Seoul', 'status': 'COMPLETED', 'country': 'South Korea', 'facility': 'Samsung Medical Center', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}], 'centralContacts': [{'name': 'Alyssa Voelker-Christy', 'role': 'CONTACT', 'email': 'nadira@insightec.com', 'phone': '817-948-5219'}], 'overallOfficials': [{'name': 'Manmeet Ahluwalia, MD, MBA', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Miami Cancer Institute, Baptist Health South Florida'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'InSightec', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}