Ignite Creation Date:
2025-12-24 @ 4:27 PM
Ignite Modification Date:
2025-12-28 @ 4:11 AM
Study NCT ID:
NCT01009866
Status:
TERMINATED
Last Update Posted:
2015-03-20
First Post:
2009-11-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of Immunotoxin, MR1-1
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001932', 'term': 'Brain Neoplasms'}, {'id': 'D001254', 'term': 'Astrocytoma'}, {'id': 'D004806', 'term': 'Ependymoma'}, {'id': 'D004194', 'term': 'Disease'}], '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': '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': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 9}}, 'statusModule': {'whyStopped': 'low accrual', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2006-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-03', 'completionDateStruct': {'date': '2012-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-03-18', 'studyFirstSubmitDate': '2009-11-06', 'studyFirstSubmitQcDate': '2009-11-06', 'lastUpdatePostDateStruct': {'date': '2015-03-20', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2009-11-09', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximum tolerated dose and dose limiting toxicity', 'timeFrame': 'continual'}], 'secondaryOutcomes': [{'measure': 'Disease Progression', 'timeFrame': 'continual'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Malignant brain tumor', 'GBM', 'recurrent brain tumor', 'Supratentorial malignant brain tumor', 'astrocytomas', 'ependymomas', 'Residual, progressive, or recurrent supratentorial malignant brain tumor based on imaging studies with measurable', 'disease (>0.5cm).'], 'conditions': ['Supratentorial Malignant Brain Tumor']}, 'descriptionModule': {'briefSummary': 'Purpose of the study:\n\nPrimary Objective: Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of MR1-1KDEL when delivered intracerebrally by convection-enhanced delivery (CED) in patients with supratentorial malignant brain tumors.\n\nSecondary Objective: Document any radiographic responses associated with intracerebral CED of MR1-1KDEL.\n\nHypothesis: The investigators believe that MR1-1KDEL will be an effective anti-tumor agent for patients with supratentorial malignant brain tumors when delivered by CED.\n\nDesign \\& procedures: This protocol is designed primarily to determine the MTD and DLT of a novel, tumor-specific immunotoxin, MR1-1KDEL. MR1-1KDEL will be delivered intracerebrally by CED using 2 intracerebral catheters with at least one catheter placed within the enhancing portion of the tumor. 124I-labeled albumin will be co-infused with gadolinium and PET and MRI images will be obtained at the conclusion of the infusion to monitor volume of drug distribution and leakage into the CSF space.\n\nBased on preclinical toxicity studies, the starting total drug dose will be 0.5μg (500ng) which represents 1/20th of the MTD in rats. The infusion flow rate will be fixed at 0.5 mL/h from each of two to four catheters. A total of 144 mLs of drug solution will be delivered over 72 hours. MR1-1KDEL dose escalation will be accomplished by increasing drug concentration allowing flow rate and infusion volume to remain unchanged. Drug dose will be doubled in successive cohorts so long as DLTs are not observed as follows: 25 ng/mL (2.4 μg)(starting dose); 50ng/mL (4.8μg); 100 ng/mL (9.6μg); 200ng/mL (19.2μg); 400 ng/mL (38.4μg); 800 ng/mL (76.8μg); and 1600 ng/mL (153.6μg). At least 3 patients will be enrolled in each cohort. All patients in a given cohort will be observed for at least two weeks following infusion of the study drug before patients in the next cohort are treated. If no patients in a given cohort experience a DLT, the dose will be escalated in the next cohort. If 1 out of 3 patients in a given cohort experience DLT, 3 additional patients will be entered in that cohort. If 2 patients develop a DLT in any cohort of 3 or 6 patients, the previous dose will be declared the MTD. Patients will be followed at 1, 3, 6, 9, 12 month intervals for toxicity and adverse events, radiographic response, and survival. Patients will be off study when progressive disease is documented.\n\nRisk/benefit assessment: This is an experimental study and unforeseeable or unexpected risks may be involved.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Residual, progressive, or recurrent supratentorial malignant brain tumor based on imaging studies with measurable disease (\\>0.5cm).\n* Patient will have completed some form of radiation therapy prior to toxin treatment.\n* Karnofsky Performance score \\>70.\n* The presence of the target antigen, EGFRvIII, must be identified on tumor tissue by immunohistochemistry.\n* Platelet count \\> 100 x 109/L; PTT and PT \\< 120% of normal range.\n* Creatinine \\< 120% of normal range.\n* Total bilirubin, SGOT, SGPT,alkaline phosphatase \\< 300% of normal range.\n\nExclusion Criteria:\n\n* Patients who are pregnant, breast-feeding, or unwilling to practice an effective method of birth control.\n* Patients with known potentially anaphylactic allergic reactions to iodine or gadolinium-DTPA.\n* Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (specifically pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods or plates).\n* Patients that have not recovered from the toxic effects of prior chemotherapy and/or radiation therapy.\n* Patients with an impending, life-threatening cerebral herniation syndrome.\n* Patients with subependymal or CSF disease.\n* Patients who are under the age of 18 years.'}, 'identificationModule': {'nctId': 'NCT01009866', 'acronym': 'MR1-1', 'briefTitle': 'Study of Immunotoxin, MR1-1', 'organization': {'class': 'OTHER', 'fullName': 'Duke University'}, 'officialTitle': 'Phase I Study of Immunotoxin, MR1-1', 'orgStudyIdInfo': {'id': 'Pro00011617'}, 'secondaryIdInfos': [{'id': 'P50NS020023', 'link': 'https://reporter.nih.gov/quickSearch/P50NS020023', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'MR1-1', 'description': 'All subjects are enrolled onto this arm. All subjects will receive MR1-1.', 'interventionNames': ['Biological: MR1-1']}], 'interventions': [{'name': 'MR1-1', 'type': 'BIOLOGICAL', 'otherNames': ['MR1-1KDEL'], 'description': 'Based on preclinical toxicity studies, the starting total drug dose will be 0.5μg (500ng) which represents 1/20th of the MTD in rats. The infusion flow rate will be fixed at 0.5 mL/h from each of two catheters. A total of 96 mLs of drug solution will be delivered over 96 hours. MR1-1KDEL dose escalation will be accomplished by increasing drug concentration allowing flow rate and infusion volume to remain unchanged. Drug dose will be doubled in successive cohorts so long as DLTs are not observed as follows: 25 ng/mL (2.4 μg)(starting dose); 50ng/mL (4.8μg); 100 ng/mL (9.6μg); 200ng/mL (19.2μg); 400 ng/mL (38.4μg); 800 ng/mL (76.8μg); and 1600 ng/mL (153.6μg).', 'armGroupLabels': ['MR1-1']}]}, 'contactsLocationsModule': {'locations': [{'zip': '27710', 'city': 'Durham', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Duke University Health System', 'geoPoint': {'lat': 35.99403, 'lon': -78.89862}}], 'overallOfficials': [{'name': 'Annick Desjardins, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Duke Health'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Darell D. Bigner, MD, PhD', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of Neurological Disorders and Stroke (NINDS)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Director, The Preston Robert Tisch Brain Tumor Center at Duke', 'investigatorFullName': 'Darell D. Bigner, MD, PhD', 'investigatorAffiliation': 'Duke University'}}}}