Ignite Creation Date:
2025-12-25 @ 4:58 AM
Ignite Modification Date:
2025-12-26 @ 3:58 AM
Study NCT ID:
NCT01128218
Status:
COMPLETED
Last Update Posted:
2023-11-30
First Post:
2010-05-13
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
A Study of the Specificity and Sensitivity of 5- Aminolevulinic Acid (ALA) Fluorescence in Malignant Brain Tumors
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001932', 'term': 'Brain Neoplasms'}, {'id': 'D005910', 'term': 'Glioma'}, {'id': 'D005909', 'term': 'Glioblastoma'}], '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': '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': 'D001254', 'term': 'Astrocytoma'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000622', 'term': 'Aminolevulinic Acid'}], 'ancestors': [{'id': 'D007982', 'term': 'Levulinic Acids'}, {'id': 'D007651', 'term': 'Keto Acids'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'blokaitis@siumed.edu', 'phone': '217.545.9737', 'title': 'Barbara Lokaitis, BA, CCRP / Senior Clinical Research Coordinator', 'organization': 'SIU Medicine'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': '6 years', 'eventGroups': [{'id': 'EG000', 'title': 'Phase 1, Dose Level 1 (10mg/kg)', 'description': 'Phase 1 Dose Level 1: Participants were given a one-time, single-dose administration of oral 10mg/kg Aminolevulinic Acid (5-ALA)', 'otherNumAtRisk': 3, 'deathsNumAtRisk': 3, 'otherNumAffected': 0, 'seriousNumAtRisk': 3, 'deathsNumAffected': 1, 'seriousNumAffected': 2}, {'id': 'EG001', 'title': 'Phase 1, Dose Level 2 (20mg/kg)', 'description': 'Phase 1 Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)', 'otherNumAtRisk': 3, 'deathsNumAtRisk': 3, 'otherNumAffected': 0, 'seriousNumAtRisk': 3, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Phase 1, Dose Level 3 (30mg/kg)', 'description': 'Phase 1 Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)', 'otherNumAtRisk': 3, 'deathsNumAtRisk': 3, 'otherNumAffected': 0, 'seriousNumAtRisk': 3, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG003', 'title': 'Phase 1, Dose Level 4 (40mg/kg)', 'description': 'Phase 1 Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)', 'otherNumAtRisk': 4, 'deathsNumAtRisk': 4, 'otherNumAffected': 0, 'seriousNumAtRisk': 4, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG004', 'title': 'Phase 1, Dose Level 5 (50mg/kg)', 'description': 'Phase 1 Dose Level 5: Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)', 'otherNumAtRisk': 6, 'deathsNumAtRisk': 6, 'otherNumAffected': 0, 'seriousNumAtRisk': 6, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG005', 'title': 'Phase 2 (40mg/kg)', 'description': 'Phase 2 Dose (40mg/kg): Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)', 'otherNumAtRisk': 14, 'deathsNumAtRisk': 14, 'otherNumAffected': 0, 'seriousNumAtRisk': 14, 'deathsNumAffected': 0, 'seriousNumAffected': 2}], 'seriousEvents': [{'term': 'death', 'notes': 'The patient was coded secondary to the ventricular tachycardia change to ventricular fibrillation and asystole in 20 seconds.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 4, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG005', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'non-applicable'}, {'term': 'scalp wound abscess', 'notes': 'Admitted to hospital for an infected cranial wound. Subject seen by infectious disease specialist Incision and drainage of cranial wound, removal of cranial bone flap, and revision of cranial wound done.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 4, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG005', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'non-applicable'}, {'term': 'severe cerebral edema', 'notes': 'blown pupils; intubated; increased cerebral edema; evidence of increased density in the basilar subarachnoid spaces and did not show true subarachnoid hemorrhage; culture positive for Gram Negative Rods.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 4, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG005', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'non-applicable'}, {'term': 'partial seizure', 'notes': '"Had a partial seizure today despite Keppra prophylaxis."', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 4, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG005', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'non-applicable'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Establish a Safe Dose for Oral 5-ALA Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}, {'value': '3', 'groupId': 'OG002'}, {'value': '4', 'groupId': 'OG003'}, {'value': '6', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 1 Dose Level 1 (10mg/kg)', 'description': 'Phase 1 Dose Level 1: Participants were given a one-time, single-dose administration of oral 10mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'OG001', 'title': 'Phase 1 Dose Level 2 (20mg/kg)', 'description': 'Phase 1 Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'OG002', 'title': 'Phase 1 Dose Level 3 (30mg/kg)', 'description': 'Phase 1 Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'OG003', 'title': 'Phase 1 Dose Level 4 (40mg/kg)', 'description': 'Phase 1 Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'OG004', 'title': 'Phase 1 Dose Level 5 (50mg/kg)', 'description': 'Phase 1 Dose Level 5: Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}, {'value': '0', 'groupId': 'OG003'}, {'value': '0', 'groupId': 'OG004'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6 months', 'description': 'Dose escalation from 10mg/kg to 50mg/kg to determine optimal 5-ALA dose', 'unitOfMeasure': 'Dose Limiting Toxicity', 'reportingStatus': 'POSTED', 'populationDescription': 'There were no dose limiting toxicities observed at any dose level arm. Therefore, the 40mg/kg dose was arbitrarily chosen for the phase 2 portion of the study.'}, {'type': 'PRIMARY', 'title': 'Determine the Sensitivity, Specificity, and Positive Predictive Value of 5-ALA Mediated Fluorescence for Malignant Glioma Tissue in the Brain.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}]}, {'units': 'Biopsies', 'counts': [{'value': '28', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 2 Dose Level 1 (40mg/kg)', 'description': 'A single arm in this open-label study where all patients are treated with the study drug - 5-aminolevulinic acid. Areas of the brain that are fluorescent and areas that are not fluorescent are evaluated for presence of tumor cells\n\nTumor fluorescence: Oral Phase 2 dose: 40mg/kg.'}], 'classes': [{'title': 'Sensitivity', 'categories': [{'measurements': [{'value': '63.64', 'groupId': 'OG000'}]}]}, {'title': 'Specificity', 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'Positive Predictive Value', 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'Negative Predictive Value', 'categories': [{'measurements': [{'value': '42.86', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Baseline', 'description': "The neurosurgeon will take two small biopsies per patient from areas identified as obvious tumor and areas in the wall of the resection cavity that were judged to be normal, non-eloquent brain. A neuropathologist will review all biopsy specimens, including those taken from the solid tumor. Pathologic confirmation of tumor type will be made by the study reference neuropathologist.\n\nWe assessed 5-ALA's resulting fluorescence for distinguishing tumor within the brain, where\n\nTrue Positive: Fluorescence showing Tumor and Biopsy result Tumor False Positive: Fluorescence showing Tumor and Biopsy result No Tumor True Negative: No Fluorescence and Biopsy result No Tumor False Negative: No Fluorescence and Biopsy result Tumor\n\nThese values represent the characteristics of 5-ALA aka its ability to distinguish tumor from non-tumor. From these parameters we determined sensitivity, specificity and the positive and negative predictive values.", 'unitOfMeasure': 'Percentage', 'reportingStatus': 'POSTED', 'typeUnitsAnalyzed': 'Biopsies', 'denomUnitsSelected': 'Biopsies', 'populationDescription': 'Assessing sensitivity, specificity, positive predictive value, and negative predictive value in Phase 2 Study Population of N=14 Patients at 40 mg/kg Dose'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': "Assess 5-ALA's Resulting Fluorescence for Distinguishing Tumor Within the Brain", 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}]}, {'units': 'Biopsies', 'counts': [{'value': '28', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 2 Dose Level 1 (40mg/kg)', 'description': 'A single arm in this open-label study where all patients are treated with the study drug - 5-aminolevulinic acid. Areas of the brain that are fluorescent and areas that are not fluorescent are evaluated for presence of tumor cells\n\nTumor fluorescence: Oral Phase 2 dose: 40mg/kg.'}], 'classes': [{'title': 'True Positives', 'categories': [{'measurements': [{'value': '14', 'groupId': 'OG000'}]}]}, {'title': 'True Negatives', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}]}]}, {'title': 'False Positives', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'False Negatives', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Baseline', 'description': "Under blue light, the neurosurgeon will take two small biopsies per patient from areas identified as obvious tumor (fluorescent) and areas in the wall of the resection cavity that were judged to be normal (but possibly edematous), non-eloquent brain (non-fluorescent). A neuropathologist will review all biopsy specimens, including those taken from the solid tumor. Pathologic confirmation of tumor type will be made by the study reference neuropathologist.\n\nWe assessed 5-ALA's resulting fluorescence for distinguishing tumor within the brain, where\n\nTrue Positive: Fluorescence showing Tumor and Biopsy result Tumor False Positive: Fluorescence showing Tumor and Biopsy result No Tumor True Negative: No Fluorescence and Biopsy result No Tumor False Negative: No Fluorescence and Biopsy result Tumor\n\nThese values represent the characteristics of 5-ALA aka its ability to distinguish tumor from non-tumor.", 'unitOfMeasure': 'Biopsies', 'reportingStatus': 'POSTED', 'typeUnitsAnalyzed': 'Biopsies', 'denomUnitsSelected': 'Biopsies', 'populationDescription': 'Phase 2 Study Population of N=14 Patients at 40 mg/kg Dose'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Phase 1 Dose Level 1 (10mg/kg)', 'description': 'Dose Level 1: Participants were given a one-time, single-dose administration of oral10mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'FG001', 'title': 'Phase 1 Dose Level 2 (20mg/kg)', 'description': 'Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'FG002', 'title': 'Phase 1 Dose Level 3 (30mg/kg)', 'description': 'Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'FG003', 'title': 'Phase 1 Dose Level 4 (40mg/kg)', 'description': 'Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'FG004', 'title': 'Phase 1 Dose Level 5 (50mg/kg)', 'description': 'Dose Level 5: Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'FG005', 'title': 'Phase 2 (40mg/kg)', 'description': 'Phase 2 (40mg/kg): Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '4'}, {'groupId': 'FG004', 'numSubjects': '6'}, {'groupId': 'FG005', 'numSubjects': '14'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '4'}, {'groupId': 'FG004', 'numSubjects': '6'}, {'groupId': 'FG005', 'numSubjects': '14'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}, {'groupId': 'FG005', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '4', 'groupId': 'BG003'}, {'value': '6', 'groupId': 'BG004'}, {'value': '14', 'groupId': 'BG005'}, {'value': '33', 'groupId': 'BG006'}]}], 'groups': [{'id': 'BG000', 'title': 'Phase 1 Dose Level 1 (10mg/kg)', 'description': 'Phase 1 Dose Level 1: Participants were given a one-time, single-dose administration of oral 10mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'BG001', 'title': 'Phase 1 Dose Level 2 (2omg/kg)', 'description': 'Phase 1 Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'BG002', 'title': 'Phase 1 Dose Level 3 (30mg/kg)', 'description': 'Phase 1 Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'BG003', 'title': 'Phase 1 Dose Level 4 (40mg/kg)', 'description': 'Phase 1 Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'BG004', 'title': 'Phase 1 Dose Level 5 (50mg/kg)', 'description': 'Phase 1 Dose Level 1: Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'BG005', 'title': 'Phase 2 (40mg/kg)', 'description': 'Phase 2: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)'}, {'id': 'BG006', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '0', 'groupId': 'BG005'}, {'value': '0', 'groupId': 'BG006'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}, {'value': '6', 'groupId': 'BG004'}, {'value': '6', 'groupId': 'BG005'}, {'value': '19', 'groupId': 'BG006'}]}, {'title': '>=65 years', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '3', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '8', 'groupId': 'BG005'}, {'value': '14', 'groupId': 'BG006'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '64', 'groupId': 'BG000', 'lowerLimit': '32', 'upperLimit': '87'}, {'value': '61', 'groupId': 'BG001', 'lowerLimit': '54', 'upperLimit': '74'}, {'value': '63', 'groupId': 'BG002', 'lowerLimit': '62', 'upperLimit': '67'}, {'value': '71', 'groupId': 'BG003', 'lowerLimit': '63', 'upperLimit': '77'}, {'value': '52.5', 'groupId': 'BG004', 'lowerLimit': '44', 'upperLimit': '62'}, {'value': '56.36', 'groupId': 'BG005', 'lowerLimit': '21', 'upperLimit': '84'}, {'value': '58.63', 'groupId': 'BG006', 'lowerLimit': '21', 'upperLimit': '87'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}, {'value': '3', 'groupId': 'BG004'}, {'value': '8', 'groupId': 'BG005'}, {'value': '16', 'groupId': 'BG006'}]}, {'title': 'Male', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '3', 'groupId': 'BG003'}, {'value': '3', 'groupId': 'BG004'}, {'value': '6', 'groupId': 'BG005'}, {'value': '17', 'groupId': 'BG006'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '0', 'groupId': 'BG005'}, {'value': '1', 'groupId': 'BG006'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '3', 'groupId': 'BG003'}, {'value': '6', 'groupId': 'BG004'}, {'value': '14', 'groupId': 'BG005'}, {'value': '32', 'groupId': 'BG006'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '0', 'groupId': 'BG005'}, {'value': '0', 'groupId': 'BG006'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '0', 'groupId': 'BG005'}, {'value': '0', 'groupId': 'BG006'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '0', 'groupId': 'BG005'}, {'value': '0', 'groupId': 'BG006'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '0', 'groupId': 'BG005'}, {'value': '0', 'groupId': 'BG006'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '0', 'groupId': 'BG005'}, {'value': '1', 'groupId': 'BG006'}]}, {'title': 'White', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '4', 'groupId': 'BG003'}, {'value': '6', 'groupId': 'BG004'}, {'value': '14', 'groupId': 'BG005'}, {'value': '32', 'groupId': 'BG006'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '0', 'groupId': 'BG005'}, {'value': '0', 'groupId': 'BG006'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '0', 'groupId': 'BG005'}, {'value': '0', 'groupId': 'BG006'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '4', 'groupId': 'BG003'}, {'value': '6', 'groupId': 'BG004'}, {'value': '14', 'groupId': 'BG005'}, {'value': '33', 'groupId': 'BG006'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2017-01-22', 'size': 354610, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2023-04-13T12:48', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Dose escalation study'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 33}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-03', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-11', 'completionDateStruct': {'date': '2021-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-11-09', 'studyFirstSubmitDate': '2010-05-13', 'resultsFirstSubmitDate': '2023-04-13', 'studyFirstSubmitQcDate': '2010-05-20', 'lastUpdatePostDateStruct': {'date': '2023-11-30', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-11-09', 'studyFirstPostDateStruct': {'date': '2010-05-21', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2023-11-30', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': "Assess 5-ALA's Resulting Fluorescence for Distinguishing Tumor Within the Brain", 'timeFrame': 'Baseline', 'description': "Under blue light, the neurosurgeon will take two small biopsies per patient from areas identified as obvious tumor (fluorescent) and areas in the wall of the resection cavity that were judged to be normal (but possibly edematous), non-eloquent brain (non-fluorescent). A neuropathologist will review all biopsy specimens, including those taken from the solid tumor. Pathologic confirmation of tumor type will be made by the study reference neuropathologist.\n\nWe assessed 5-ALA's resulting fluorescence for distinguishing tumor within the brain, where\n\nTrue Positive: Fluorescence showing Tumor and Biopsy result Tumor False Positive: Fluorescence showing Tumor and Biopsy result No Tumor True Negative: No Fluorescence and Biopsy result No Tumor False Negative: No Fluorescence and Biopsy result Tumor\n\nThese values represent the characteristics of 5-ALA aka its ability to distinguish tumor from non-tumor."}], 'primaryOutcomes': [{'measure': 'Establish a Safe Dose for Oral 5-ALA Administration', 'timeFrame': '6 months', 'description': 'Dose escalation from 10mg/kg to 50mg/kg to determine optimal 5-ALA dose'}, {'measure': 'Determine the Sensitivity, Specificity, and Positive Predictive Value of 5-ALA Mediated Fluorescence for Malignant Glioma Tissue in the Brain.', 'timeFrame': 'Baseline', 'description': "The neurosurgeon will take two small biopsies per patient from areas identified as obvious tumor and areas in the wall of the resection cavity that were judged to be normal, non-eloquent brain. A neuropathologist will review all biopsy specimens, including those taken from the solid tumor. Pathologic confirmation of tumor type will be made by the study reference neuropathologist.\n\nWe assessed 5-ALA's resulting fluorescence for distinguishing tumor within the brain, where\n\nTrue Positive: Fluorescence showing Tumor and Biopsy result Tumor False Positive: Fluorescence showing Tumor and Biopsy result No Tumor True Negative: No Fluorescence and Biopsy result No Tumor False Negative: No Fluorescence and Biopsy result Tumor\n\nThese values represent the characteristics of 5-ALA aka its ability to distinguish tumor from non-tumor. From these parameters we determined sensitivity, specificity and the positive and negative predictive values."}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Brain Neoplasms', '5-ALA', 'Aminolevulinic acid', 'Fluorescence', 'Gliomas', 'Glioblastoma', 'Surgery'], 'conditions': ['Brain Neoplasms']}, 'referencesModule': {'references': [{'pmid': '10555843', 'type': 'BACKGROUND', 'citation': 'Keles GE, Anderson B, Berger MS. The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere. Surg Neurol. 1999 Oct;52(4):371-9. doi: 10.1016/s0090-3019(99)00103-2.'}, {'pmid': '18496181', 'type': 'BACKGROUND', 'citation': 'Sanai N, Berger MS. Glioma extent of resection and its impact on patient outcome. Neurosurgery. 2008 Apr;62(4):753-64; discussion 264-6. doi: 10.1227/01.neu.0000318159.21731.cf.'}, {'pmid': '16648043', 'type': 'BACKGROUND', 'citation': 'Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401. doi: 10.1016/S1470-2045(06)70665-9.'}, {'pmid': '19248665', 'type': 'BACKGROUND', 'citation': 'Tonn JC, Stummer W. Fluorescence-guided resection of malignant gliomas using 5-aminolevulinic acid: practical use, risks, and pitfalls. Clin Neurosurg. 2008;55:20-6. No abstract available.'}, {'pmid': '39526779', 'type': 'DERIVED', 'citation': 'Cozzens JW, Lokaitis BC, Delfino K, Hoeft A, Moore BE, Fifer AS, Amin DV, Espinosa JA, Jones BA, Acakpo-Satchivi L. A Phase 2 Sensitivity and Selectivity Study of High-Dose 5-Aminolevulinic Acid in Adult Patients Undergoing Resection of a Newly Diagnosed or Recurrent Glioblastoma. Oper Neurosurg. 2024 Nov 11;29(1):71-79. doi: 10.1227/ons.0000000000001417.'}], 'seeAlsoLinks': [{'url': 'http://www.nlm.nih.gov/medlineplus/braincancer.html', 'label': 'Brain Cancer'}, {'url': 'http://www.nlm.nih.gov/medlineplus/cancer.html', 'label': 'Cancer'}]}, 'descriptionModule': {'briefSummary': 'Extent of resection is a very important prognostic factor affecting survival in individuals diagnosed with a malignant glioma. However, the infiltrative nature of the malignant glioma tumor cells produces indistinct borders between normal and malignant tissues, and the lack of easily identifiable tumor margins confounds attempts at total resection. The investigators propose to identify the borders of malignant gliomas intraoperatively using oral 5-aminolevulinic Acid (5-ALA) which results in fluorescence of the malignant cells and thereby provide an opportunity for more complete tumor resection.\n\nWhen exogenous 5-ALA is provided at increased concentration the tumor cells will become fluorescent under ultraviolet light. This feature identifies the tumor cells intraoperatively and facilitates complete resection.\n\nData collection will include measurement of dose-limiting toxicity, tumor fluorescence, and tumor density. Data analysis will evaluate toxicity, sensitivity, and specificity of 5-ALA.\n\nFollowing completion of the phase 1 portion of this trial, an additional 14 subjects will be entered at the recommended phase 2 dose level in order to further define the above parameters at the recommended phase 2 dose level.', 'detailedDescription': 'Specific Aims:\n\nThis study is intended to investigate the utility, safety and efficacy of 5-aminolevulinic acid (5-ALA) induced brain tumor fluorescence during malignant brain tumor resection. Specifically this study is intended to:\n\nEstablish a safe dose for oral 5-ALA administration. Determine the sensitivity and specificity of 5-ALA mediated fluorescence for malignant glioma tissue in the brain.\n\nBackground and Significance:\n\nThere is a considerable body of literature that suggests that completeness of resection is a positive factor for longer term survival in individuals with malignant glioma. Unfortunately, it is often difficult to completely remove a malignant brain tumor because during surgery it is sometimes very difficult to distinguish tumor from normal brain. It would be very helpful if there would be some way to help the surgeon make this distinction. Malignant glioma tumor cells (more so than normal cells) contain the biosynthetic pathways to produce protoporphyrin from a naturally occurring amino acid, 5-aminolevulinic acid (5-ALA). Protoporphyrin is the immediate precursor to hemoglobin (it is hemoglobin without the iron atom) and is fluorescent under blue light. When exogenous 5-ALA is provided at increased concentration, protoporphyrin concentration in the malignant cell increases at a rate far greater than normal brain cells and renders the malignant cell fluorescent red under blue light. This feature distinguishes the tumor cells from normal cells intraoperatively and facilitates complete resection.\n\nRecent studies in Germany have confirmed the utility of pre-operative oral 5-ALA and intraoperative brain tumor fluorescence in aiding the resection of brain tumors in individuals with malignant brain tumors. These studies have led to oral 5-ALA to be approved for this indication by the European Medicines Agency, but oral 5-ALA has not been approved for this indication by the United States FDA. This proposal is a phase 1 and phase 2 trial that will hopefully lead to FDA approval of oral 5-ALA for intra-operative visualization of malignant brain tumors.\n\nExperimental Plan and Methods:\n\nIn the phase 1 part of this proposed study, a minimum of 3 to a maximum of 19 patients will be administered oral 5-ALA 4 hours prior to surgery in cohorts of 3 at five escalating doses of 5-ALA (10, 20, 30, 40, or 50 mg/kg).\n\nThe following data will be collected:\n\n* Dose-limiting toxicity data; i.e., nausea, vomiting, liver function, photo-sensitivity\n* Tumor fluorescence assessed by neurosurgeon\n* Tumor density from biopsies obtained by the neurosurgeon in will be assessed by neuropathology (Solid tumor, Tumor mixed infiltrating normal brain, No tumor)\n\nThis trial will evaluate:\n\n* single dose toxicity of oral 5-ALA given pre-operatively;\n* sensitivity and specificity of 5-ALA - Protoporphyrin IX (Pp IX) as an intraoperative fluorescent detection agent and aid for resection of tumor tissue remaining in the walls of the resection cavity of primary and recurrent malignant brain tumors;\n\nFollowing completion of the phase 1 portion of this trial, an additional 14 subjects will be entered at the recommended phase 2 dose level in order to further define the above parameters at the recommended phase 2 dose level.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients must have clinically documented primary brain tumor for which resection is clinically indicated.\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of 5-ALA in patients \\<18 years of age, children are excluded from this study but will be eligible for future pediatric phase 1 single-agent trials\n* ECOG (Eastern Cooperative Oncology Group) performance status \\<2 (Karnofsky \\>60%)\n* Normal organ and marrow function as defined below:\n\n * Leukocytes \\> 3,000/mcL (microliter)\n * Absolute neutrophil count \\> 1,500/mcL\n * Platelets \\> 100,000/mcL\n * Total bilirubin within normal institutional limits AST (aspartate aminotransferase) (SGOT)/ALT (alanine transaminase) (SGPT) \\< 2.5 X institutional upper limit of normal\n * Creatinine within normal institutional limits OR Creatinine clearance \\> 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal\n* Agreement by women of child-bearing potential and men to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation\n* Ability to understand and the willingness to sign a written informed consent document\n\nExclusion Criteria:\n\n* Patients may not be receiving any other investigational agents at the time of entry into the study\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-ALA\n* Personal or family history of porphyrias\n* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study because 5-ALA is of unknown teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 5-ALA, breastfeeding should be discontinued if the mother is treated with 5-ALA'}, 'identificationModule': {'nctId': 'NCT01128218', 'briefTitle': 'A Study of the Specificity and Sensitivity of 5- Aminolevulinic Acid (ALA) Fluorescence in Malignant Brain Tumors', 'organization': {'class': 'OTHER', 'fullName': 'Southern Illinois University'}, 'officialTitle': 'A Phase 1 and 2 Study of 5-aminolevulinic Acid (5-ALA) to Enhance Visualisation and Resection of Malignant Glial Tumors of the Brain', 'orgStudyIdInfo': {'id': 'COZ-SIU 10-002-1'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Phase 1 Dose Level 1 (10mg/kg)', 'description': 'Dose Level 1: Participants were given a one-time, single-dose administration of oral 10mg/kg Aminolevulinic Acid (5-ALA)', 'interventionNames': ['Drug: Tumor fluorescence']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1 Dose Level 2 (20mg/kg)', 'description': 'Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)', 'interventionNames': ['Drug: Tumor fluorescence']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1 Dose level 3 (30mg/kg)', 'description': 'Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)', 'interventionNames': ['Drug: Tumor fluorescence']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1 Dose level 4 (40mg/kg)', 'description': 'Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)', 'interventionNames': ['Drug: Tumor fluorescence']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1 Dose level 5 (50mg/kg)', 'description': 'Dose Level 5: Participants were given a one-time, single-dose administration of 50mg/kg Aminolevulinic Acid (5-ALA)', 'interventionNames': ['Drug: Tumor fluorescence']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 2 (40mg/kg)', 'description': 'Phase 2: Participants were given a one-time, single-dose administration of 40mg/kg Aminolevulinic Acid (5-ALA)', 'interventionNames': ['Drug: Tumor fluorescence']}], 'interventions': [{'name': 'Tumor fluorescence', 'type': 'DRUG', 'otherNames': ['5-ALA', '5-aminolevulinic acid'], 'description': 'Oral doses in phase 1 study of 10mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg and 50 mg/kg.\n\nRecommended oral dose of phase 1 will be used in phase 2', 'armGroupLabels': ['Phase 1 Dose Level 1 (10mg/kg)', 'Phase 1 Dose Level 2 (20mg/kg)', 'Phase 1 Dose level 3 (30mg/kg)', 'Phase 1 Dose level 4 (40mg/kg)', 'Phase 1 Dose level 5 (50mg/kg)', 'Phase 2 (40mg/kg)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '62702', 'city': 'Springfield', 'state': 'Illinois', 'country': 'United States', 'facility': 'Southern Illinois University School of Medicine', 'geoPoint': {'lat': 39.80172, 'lon': -89.64371}}], 'overallOfficials': [{'name': 'Jeffrey W Cozzens, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Southern Illinois University School of Medicine'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Southern Illinois University', 'class': 'OTHER'}, 'collaborators': [{'name': 'DUSA Pharmaceuticals, Inc.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}