Ignite Creation Date:
2025-12-24 @ 2:55 PM
Ignite Modification Date:
2026-02-25 @ 7:42 AM
Study NCT ID:
NCT03363659
Status:
TERMINATED
Last Update Posted:
2024-10-03
First Post:
2017-11-30
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2023-07-21', 'type': 'ACTUAL'}}}}, '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': 'D004221', 'term': 'Disulfiram'}, {'id': 'D005942', 'term': 'Gluconates'}, {'id': 'D000077204', 'term': 'Temozolomide'}], 'ancestors': [{'id': 'D004050', 'term': 'Ditiocarb'}, {'id': 'D013859', 'term': 'Thiocarbamates'}, {'id': 'D002219', 'term': 'Carbamates'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D004220', 'term': 'Disulfides'}, {'id': 'D013440', 'term': 'Sulfides'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D013400', 'term': 'Sugar Acids'}, {'id': 'D006880', 'term': 'Hydroxy Acids'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D003606', 'term': 'Dacarbazine'}, {'id': 'D014226', 'term': 'Triazenes'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'karen.cheek@aah.org', 'phone': '414 778 4345', 'title': 'Manager of Oncology research', 'organization': 'Advocate Aurora Health'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': 'Reportable adverse events will be tracked for 30 days after the last dose of DSF-Cu. Survival for participants was followed for up to 2 years.', 'description': '13 participants started the treatment and the only ones assessed for adverse events. All participants were included in all cause mortality.', 'eventGroups': [{'id': 'EG000', 'title': 'Open Label', 'description': 'Open-Label, Single Arm Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients with Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme', 'otherNumAtRisk': 13, 'deathsNumAtRisk': 15, 'otherNumAffected': 0, 'seriousNumAtRisk': 13, 'deathsNumAffected': 11, 'seriousNumAffected': 1}], 'seriousEvents': [{'term': 'Hepatic Failure', 'notes': '60 year old female with a history of Glioblastoma multiforme, presented with increased fatigue and new onset jaundice. Liver biopsy, which favored drug-induced liver injury likely due to chemotherapy agents.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (12.0)'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': '6 Months Progression Free Survival (PFS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Open Label', 'description': 'Open-Label, Single Arm Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients with Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '6 months', 'description': 'To determine 6 month PFS of patients with unmethylated glioblastoma treated with DSF-Cu in combination with concurrent radiation and temozolomide. This was assessed by the number of participants who did not have disease progression and were alive at 6 months.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Overall Survival', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Open Label', 'description': 'Open-Label, Single Arm Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients with Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme'}], 'classes': [{'title': '1 Year', 'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}]}]}, {'title': '2 Years', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '1 and 2 years', 'description': 'Overall Survival will be assessed as a number of participants alive at 1 and 2 years.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': '2 participants are not included here because 1 was a screen fail and 1 withdrew before starting treatment.'}, {'type': 'SECONDARY', 'title': 'Quality of Life (QOL)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Open Label', 'description': 'Open-Label, Single Arm Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients with Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme'}], 'timeFrame': '1 year', 'description': 'Edmonton Symptom Assessment System - Revised (ESAS-r) questionnaire', 'reportingStatus': 'POSTED', 'populationDescription': 'Disease progression or required dose modification from all participants took them all off the study. No data was collected.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Open Label', 'description': 'Open-Label, Single Arm Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients with Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'Of 15 subjects consented, 1 subject was a screen fail and 1 subject withdrew before any planned intervention.', 'groupId': 'FG000', 'numSubjects': '15'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Screen fail', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'First subject enrollment 28th March 2018. Subjects screened at neuro-oncology MDCC (Multi-disciplinary cancer clinic) and enrolled at neuro-oncology clinic.\n\nStudy closed 13th January 2022.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Open Label', 'description': 'Open-Label, Single Arm Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients with Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme.\n\nDSF will be given at 125 mg (half of a 250 mg capsule) two times daily with meals. Cu gluconate will be taken with each dose of DSF at a dose of 2 mg (one capsule/tablet). The DSF total daily dose will be 250 mg per day, as lower dose may be associated with a higher MGMT inhibitory effect.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'BG000'}]}], 'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '12', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': '15 subjects consented, Age data was not collected for 2 participants - 1 subject was a screen fail and 1 subject withdrew before any planned intervention.'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '12', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'Both men and women and members of all races and ethnic groups are eligible for this trial', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'BG000'}]}], 'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '14', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '15', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': '15 subjects consented, 1 subject was a screen fail and 1 subject withdrew before any planned intervention.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-01-17', 'size': 1020482, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2023-06-28T13:17', 'hasProtocol': True}, {'date': '2021-03-22', 'size': 588041, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_001.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2023-06-01T12:26', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 15}}, 'statusModule': {'whyStopped': 'Investigator decision', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2018-03-28', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-01', 'completionDateStruct': {'date': '2022-01-13', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-10-01', 'studyFirstSubmitDate': '2017-11-30', 'resultsFirstSubmitDate': '2023-06-28', 'studyFirstSubmitQcDate': '2017-11-30', 'lastUpdatePostDateStruct': {'date': '2024-10-03', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-09-05', 'studyFirstPostDateStruct': {'date': '2017-12-06', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2023-09-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-01-13', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '6 Months Progression Free Survival (PFS)', 'timeFrame': '6 months', 'description': 'To determine 6 month PFS of patients with unmethylated glioblastoma treated with DSF-Cu in combination with concurrent radiation and temozolomide. This was assessed by the number of participants who did not have disease progression and were alive at 6 months.'}, {'measure': 'Overall Survival', 'timeFrame': '1 and 2 years', 'description': 'Overall Survival will be assessed as a number of participants alive at 1 and 2 years.'}], 'secondaryOutcomes': [{'measure': 'Quality of Life (QOL)', 'timeFrame': '1 year', 'description': 'Edmonton Symptom Assessment System - Revised (ESAS-r) questionnaire'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Glioblastoma', 'Glioblastoma Multiforme', 'Anaplastic Glioma', 'Unmethylated'], 'conditions': ['Glioblastoma', 'Glioblastoma Multiforme']}, 'descriptionModule': {'briefSummary': 'One of Disulfiram antitumor effects suggested in preclinical studies is MGMT (methyl-guanine-methyl-transferase) inhibition. Disulfiram MGMT inhibitory effect is enhanced by addition of Copper. This study evaluates the impact of Disulfiram (DSF) + Copper (Cu) combination when added to standard Temozolomide in the treatment of unmethylated Glioblastoma Multiforme (GBM) patients.', 'detailedDescription': 'Glioblastoma is the most common malignant primary brain tumor and one of the most devastating cancers. The current standard of care for glioblastoma includes maximal safe resection followed by radiotherapy and temozolomide, which results in a median progression-free survival of less than 7 months, and median overall survival (OS) of less than 15 months. Moreover, patients with unmethylated glioblastoma respond poorly to this current standard treatment. This clinical trial evaluates the potential role of continuous, upfront use of Disulfiram in combination with Copper gluconate in enhancing temozolomide effect in the treatment of unmethylated Glioblastoma multiforme (GBM) patients.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Age 18 or older\n* Diagnosis of histologically confirmed glioblastoma (WHO grade IV). Subjects with an original histologic diagnosis of low grade glioma or anaplastic glioma (WHO grade II or III) are eligible if a subsequent histological diagnosis of glioblastoma is made\n* Patients whose tumor is determined to be unmethylated\n* Patients with incomplete resection as determined by residual, measurable gadolinium or contrast-enhancing lesion or lesions\n* Recent resection of glioblastoma within 4 weeks of study entry. Patients who have only had a tumor biopsy and who are considered unresectable are eligible (but based on the study accrual this subset of patients with unresectable tumor may be considered for separate analysis)\n* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤ 2 (see appendix A)\n* Willing to remain abstinent from consuming alcohol while on DSF\n* No prior radiation or chemotherapy\n* Meets the following laboratory criteria:\n\n * Absolute neutrophil count ≥ 1,500/mcL (microliter)\n * Platelets ≥ 100,000/mcL\n * Hemoglobin \\> 10.0 g/dL (grams/deciliter) (transfusion and/or ESA (erythropoiesis-stimulating agent) allowed)\n * Total bilirubin and alkaline phosphatase ≤ 2x institutional upper limit of normal (ULN)\n * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\< 3 x ULN\n * Blood urea nitrogen (BUN) and creatinine \\< 1.5 x ULN\n* Able to take oral medication\n* Able to understand and willing to sign an institutional review board (IRB)-approved written informed consent document (legally authorized representative permitted)\n\nExclusion Criteria:\n\n* Radiographic evidence of leptomeningeal dissemination, extensive intraparenchymal dissemination, infratentorial tumor, or metastatic disease to sites remote from the supratentorial brain\n* Enrolled in another clinical trial testing a novel therapy or drug\n* Received prior radiation therapy or chemotherapy for glioblastoma\n* History of allergic reaction/hypersensitivity to DSF (without alcohol) or copper.\n* Treatment with the following medications that may interfere with metabolism of DSF: warfarin (unless otherwise chosen by the study PI who will actively adjust Coumadin dose to consistently maintain a safe, therapeutic international normalized ratio (INR) \\< 3, theophylline, amitriptyline, isoniazid, metronidazole, phenytoin, phenobarbital, chlorzoxazone, halothane, imipramine, chlordiazepoxide, diazepam. (Note: lorazepam and oxazepam are not affected by the P450 system and are not contraindicated with DSF).\n* Active severe hepatic or renal disease\n* Grade 2 or higher peripheral neuropathy or ataxia per NCI CTCAE version 4.0 (2009)\n* History of idiopathic seizure disorder schizophrenia, or psychosis unrelated to glioblastoma, corticosteroid, or anti-epileptic medications\n* History of Wilson's or Gilbert's disease\n* Current excessive use of alcohol"}, 'identificationModule': {'nctId': 'NCT03363659', 'briefTitle': 'Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme', 'organization': {'class': 'OTHER', 'fullName': 'Wake Forest University Health Sciences'}, 'officialTitle': 'A Phase II, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients With Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme', 'orgStudyIdInfo': {'id': '17.56'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'DSF-Cu with temozolomide and radiation', 'description': 'Disulfiram (DSF; oral) / copper gluconate (Cu; oral) dosed at 125 mg / 2 mg, twice daily. Temozolomide will be administered following the standard Stupp protocol at a dose of 75 mg/m2 for 42 days with concurrent radiation therapy. Temozolomide maintenance dose will be 150 mg/m2 once daily on Days 1-5 of every 28-day cycle while DSF-Cu is continued twice daily, as tolerated, for the duration of the Temozolomide adjuvant treatment. Patients demonstrating continued benefit from the adjuvant temozolomide after 6 cycles can continue treatment to a maximum of 12 cycles', 'interventionNames': ['Drug: Disulfiram', 'Dietary Supplement: Copper gluconate', 'Drug: Temozolomide']}], 'interventions': [{'name': 'Disulfiram', 'type': 'DRUG', 'otherNames': ['Antabuse'], 'description': 'Disulfiram is taken orally, twice daily.', 'armGroupLabels': ['DSF-Cu with temozolomide and radiation']}, {'name': 'Copper gluconate', 'type': 'DIETARY_SUPPLEMENT', 'description': 'Copper gluconate is taken orally, twice daily', 'armGroupLabels': ['DSF-Cu with temozolomide and radiation']}, {'name': 'Temozolomide', 'type': 'DRUG', 'otherNames': ['Temodar, Temodal, Temcad'], 'description': 'Temozolomide is taken once daily', 'armGroupLabels': ['DSF-Cu with temozolomide and radiation']}]}, 'contactsLocationsModule': {'locations': [{'zip': '53215', 'city': 'Milwaukee', 'state': 'Wisconsin', 'country': 'United States', 'facility': "Aurora Health Care, Aurora St. Luke's Medical Center", 'geoPoint': {'lat': 43.0389, 'lon': -87.90647}}], 'overallOfficials': [{'name': 'Asadullah Khan, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Wake Forest University Health Sciences'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Wake Forest University Health Sciences', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}