Ignite Creation Date:
2025-12-26 @ 10:37 AM
Ignite Modification Date:
2025-12-26 @ 10:37 AM
Study NCT ID:
NCT01205828
Status:
TERMINATED
Last Update Posted:
2025-02-12
First Post:
2010-09-18
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
ABT-888 and Temozolomide for Liver Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006528', 'term': 'Carcinoma, Hepatocellular'}, {'id': 'D008113', 'term': 'Liver Neoplasms'}], 'ancestors': [{'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008107', 'term': 'Liver Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077204', 'term': 'Temozolomide'}, {'id': 'C521013', 'term': 'veliparib'}], 'ancestors': [{'id': 'D003606', 'term': 'Dacarbazine'}, {'id': 'D014226', 'term': 'Triazenes'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'arh29@georgetown.edu', 'phone': '202-444-8642', 'title': 'Dr. Aiwu Ruth He', 'organization': 'Georgetown University Medical Center'}, 'certainAgreement': {'restrictionType': 'GT60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': '6 months', 'eventGroups': [{'id': 'EG000', 'title': 'Temozolomide + ABT-888', 'description': 'Temozolomide and ABT-888\n\ntemozolomide + ABT-888: Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days ABT-888 40 mg BID PO Days 1-7 every 28 days\n\nPatents with stable disease or continued response to therapy will be treated and followed for a total of 6 cycles (6 months).', 'otherNumAtRisk': 16, 'otherNumAffected': 16, 'seriousNumAtRisk': 16, 'seriousNumAffected': 6}], 'otherEvents': [{'term': 'fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 7, 'numAffected': 7}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'platelet count decrease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'low neutrophil', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'low lymphocyte', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'nausea, vomit', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'nausea, vomit', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 4, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'bleeding', 'notes': 'rupture of the primary tumor', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'multiorgan failure', 'notes': 'hepato-renal syndrome from large quantity paracentesis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '4'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Clinical Benefit Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'ABT-888 and Temozolomide', 'description': 'ABT-888 40 mg daily day 1-7/28 and temozolomide 150 mg/m2/day day 1-5/28'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '8 weeks', 'description': 'complete response at any time + partial response at any time + stable disease after 8 weeks of treatment based on RECIST Criteria', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Overall Survival', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'ABT-888 and Temozolomide', 'description': 'ABT-888 40 mg daily day 1-7/28 and temozolomide 150 mg/m2/day day 1-5/28'}], 'classes': [{'categories': [{'measurements': [{'value': '13.1', 'groupId': 'OG000', 'lowerLimit': '1', 'upperLimit': '32.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '2 years', 'description': "the number of months between a patient's enrollment and his/her date of death", 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Progression Free Survival', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'ABT-888 and Temozolomide', 'description': 'ABT-888 40 mg daily day 1-7/28 and temozolomide 150 mg/m2/day day 1-5/28'}], 'classes': [{'categories': [{'measurements': [{'value': '1.9', 'groupId': 'OG000', 'lowerLimit': '1.8', 'upperLimit': '2.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '2 years', 'description': "The number of months between a patient's enrollment and his/her disease progression", 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants Who Had Grade 3 or 4 Adverse Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'ABT-888 and Temozolomide', 'description': 'ABT-888 40 mg daily day 1-7/28 and temozolomide 150 mg/m2/day day 1-5/28'}], 'classes': [{'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6 months', 'description': 'Record of all toxicities graded according to the NCI CTCAE version 3.0', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'grade 3 or 4 adverse events'}, {'type': 'SECONDARY', 'title': 'Biomarker Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Temozolomide and ABT-888 in HCC Patients', 'description': 'Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days ABT-888 40 mg BID PO Days 1-7 every 28 days\n\nTemozolomide: Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days\n\nABT-888: ABT-888 40 mg BID PO Days 1-7 every 28 days'}], 'timeFrame': '6 months', 'description': 'To evaluate biological correlation with response to ABT-888 and temozolomide, including evaluation of loss of heterozygosity (LOH) of 13q, decreased expression of or mutations in BRCA-1 or -2, and a select assortment of DNA repair genes.', 'reportingStatus': 'POSTED', 'populationDescription': 'Since the treatment showed no significant efficacy against HCC, therefore study of biomarker that predict responsiveness of the treatment was not carried out.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'ABT-888 and Temozolomide', 'description': 'ABT-888 40 mg daily day 1-7/28 and temozolomide 150 mg/m2/day day 1-5/28'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}]}, {'type': 'COMPLETED', 'achievements': [{'comment': 'Completed the first stage of the study, terminated as pre-planned due to lack of efficacy', 'groupId': 'FG000', 'numSubjects': '16'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Temozolomide + ABT-888', 'description': 'Temozolomide and ABT-888\n\ntemozolomide + ABT-888: Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days ABT-888 40 mg BID PO Days 1-7 every 28 days\n\nPatents with stable disease or continued response to therapy will be treated and followed for a total of 6 cycles (6 months).'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '13', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '61', 'groupId': 'BG000', 'lowerLimit': '40', 'upperLimit': '77'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '13', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '7', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 16}}, 'statusModule': {'whyStopped': 'Lack of efficacy', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2010-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-01', 'completionDateStruct': {'date': '2014-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-02-10', 'studyFirstSubmitDate': '2010-09-18', 'resultsFirstSubmitDate': '2015-09-07', 'studyFirstSubmitQcDate': '2010-09-18', 'lastUpdatePostDateStruct': {'date': '2025-02-12', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2016-03-02', 'studyFirstPostDateStruct': {'date': '2010-09-21', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2016-04-01', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Clinical Benefit Rate', 'timeFrame': '8 weeks', 'description': 'complete response at any time + partial response at any time + stable disease after 8 weeks of treatment based on RECIST Criteria'}], 'secondaryOutcomes': [{'measure': 'Overall Survival', 'timeFrame': '2 years', 'description': "the number of months between a patient's enrollment and his/her date of death"}, {'measure': 'Progression Free Survival', 'timeFrame': '2 years', 'description': "The number of months between a patient's enrollment and his/her disease progression"}, {'measure': 'Number of Participants Who Had Grade 3 or 4 Adverse Events', 'timeFrame': '6 months', 'description': 'Record of all toxicities graded according to the NCI CTCAE version 3.0'}, {'measure': 'Biomarker Analysis', 'timeFrame': '6 months', 'description': 'To evaluate biological correlation with response to ABT-888 and temozolomide, including evaluation of loss of heterozygosity (LOH) of 13q, decreased expression of or mutations in BRCA-1 or -2, and a select assortment of DNA repair genes.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['liver cancer', 'hepatocellular', 'temozolomide', 'veliparib'], 'conditions': ['Hepatocellular Carcinoma']}, 'referencesModule': {'references': [{'pmid': '26449224', 'type': 'DERIVED', 'citation': 'Gabrielson A, Tesfaye AA, Marshall JL, Pishvaian MJ, Smaglo B, Jha R, Dorsch-Vogel K, Wang H, He AR. Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 2015 Nov;76(5):1073-9. doi: 10.1007/s00280-015-2852-2. Epub 2015 Oct 8.'}]}, 'descriptionModule': {'briefSummary': 'This study is for people with liver cancer (also called hepatocellular carcinoma, or HCC in abbreviation).\n\nThe purpose of this study is to test the efficacy (effectiveness) of a new combination of drugs, ABT-888 and temozolomide for patients with liver cancer. Temozolomide acts by damaging deoxyribonucleic acid (DNA) in rapidly dividing cells, in other words, cancer cells. ABT-888 inhibits an enzyme called "PARP" which helps to fix damaged DNA. By inhibiting this enzyme, ABT-888 prevents cancer cells from repairing the damage caused by the temozolomide and will hopefully increase the killing of cancer cells, and decrease the tumors in the body.\n\nABT-888 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration (FDA) for use in liver cancer.\n\nThis study will help find out what effects (good and bad) the combination of drugs, temozolomide and ABT-888, has on liver cancer.\n\nThis research is being done because it is not known if ABT-888 will increase the effectiveness of temozolomide in liver cancer.', 'detailedDescription': 'Patients with hepatocellular carcinoma seen at Lombardi Cancer Center were evaluated for the eligibility of this study.\n\nThe Georgetown Lombardi Comprehensive Cancer Center was responsible for the data and safety monitoring of this trial. As this study is an investigator initiated study Phase II study utilizing a non-FDA approved drug for which the PI held the IND it was considered a high risk study which had real-time monitoring by the PI and study team and quarterly reviews by the LCCC Data and Safety Monitoring Committee (DSMC).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Pathological confirmation of HCC or noninvasive criteria following AASLD guidelines\n* Measurable or evaluable disease based on RECIST criteria\n* Progressive disease on sorafenib or intolerance to sorafenib\n* ECOG performance status 0-2\n* Child Pugh Class A or B\n* Adequate hepatic, bone marrow, and renal function\n\nExclusion Criteria:\n\n* Prior ABT-888 or other PARP inhibitor treatment\n* Anticipation of need for major surgery during the study\n* Any of the following within 6 months before enrollment: myocardial infarction, severe/unstable angina, congestive heart failure, or severe pulmonary disease\n* Women who are pregnant or lactating\n* Women and men of child-bearing potential who are not using a reliable form of contraception\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 and temozolomide\n* Concurrent malignancy (i.e. malignancy other than hepatocellular cancer) unless 1) the subject has been curatively treated and disease free for at least 2 years or 2) the cancer was non-melanoma skin cancer or early cervical cancer.\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (excluding active hepatitis B or C) or psychiatric illness/ social situations that would limit compliance with study requirements'}, 'identificationModule': {'nctId': 'NCT01205828', 'briefTitle': 'ABT-888 and Temozolomide for Liver Cancer', 'organization': {'class': 'OTHER', 'fullName': 'Georgetown University'}, 'officialTitle': 'Phase II Study of ABT-888 and Temozolomide in Patients With Advanced Hepatocellular Carcinoma (HCC) Progressing Following Sorafenib Treatment or Intolerant to Sorafenib', 'orgStudyIdInfo': {'id': '2009-268'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Temozolomide and ABT-888 in HCC patients', 'description': 'Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days ABT-888 40 mg BID PO Days 1-7 every 28 days', 'interventionNames': ['Drug: Temozolomide', 'Drug: ABT-888']}], 'interventions': [{'name': 'Temozolomide', 'type': 'DRUG', 'otherNames': ['Temodar'], 'description': 'Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days', 'armGroupLabels': ['Temozolomide and ABT-888 in HCC patients']}, {'name': 'ABT-888', 'type': 'DRUG', 'otherNames': ['Veliparib'], 'description': 'ABT-888 40 mg BID PO Days 1-7 every 28 days', 'armGroupLabels': ['Temozolomide and ABT-888 in HCC patients']}]}, 'contactsLocationsModule': {'locations': [{'zip': '20007', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': 'Lombardi Comprehensive Cancer Center at Georgetown University Medical Center', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}], 'overallOfficials': [{'name': 'Aiwu R He, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Georgetown University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Georgetown University', 'class': 'OTHER'}, 'collaborators': [{'name': 'Abbott', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}