Ignite Creation Date:
2025-12-24 @ 7:16 PM
Ignite Modification Date:
2025-12-29 @ 6:25 AM
Study NCT ID:
NCT00486603
Status:
COMPLETED
Last Update Posted:
2019-07-10
First Post:
2007-06-13
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Hydroxychloroquine, Radiation, and Temozolomide Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016543', 'term': 'Central Nervous System Neoplasms'}, {'id': 'D005909', 'term': 'Glioblastoma'}, {'id': 'D018316', 'term': 'Gliosarcoma'}], 'ancestors': [{'id': 'D009423', 'term': 'Nervous System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'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': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D006886', 'term': 'Hydroxychloroquine'}, {'id': 'D000077204', 'term': 'Temozolomide'}, {'id': 'D011827', 'term': 'Radiation'}], 'ancestors': [{'id': 'D002738', 'term': 'Chloroquine'}, {'id': 'D000634', 'term': 'Aminoquinolines'}, {'id': 'D011804', 'term': 'Quinolines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'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': 'D055585', 'term': 'Physical Phenomena'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'jfisher@jhmi.edu', 'phone': '410-955-3657', 'title': 'Director of ABTC', 'organization': 'Adult Brain Tumor Consortium'}, 'certainAgreement': {'restrictionType': 'GT60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': '3 years', 'description': 'Adverse events not serious are defined as having Grade 1 and Grade 2 severity', 'eventGroups': [{'id': 'EG000', 'title': 'Phase 1: RT+TMZ+HCQ - 200mg', 'description': 'Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday', 'otherNumAtRisk': 3, 'deathsNumAtRisk': 3, 'otherNumAffected': 3, 'seriousNumAtRisk': 3, 'deathsNumAffected': 0, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'Phase 1: RT+TMZ+HCQ - 400mg', 'description': 'Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday', 'otherNumAtRisk': 7, 'deathsNumAtRisk': 7, 'otherNumAffected': 7, 'seriousNumAtRisk': 7, 'deathsNumAffected': 0, 'seriousNumAffected': 7}, {'id': 'EG002', 'title': 'Phase 1: RT+TMZ+HCQ - 600mg', 'description': 'Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday', 'otherNumAtRisk': 3, 'deathsNumAtRisk': 3, 'otherNumAffected': 3, 'seriousNumAtRisk': 3, 'deathsNumAffected': 0, 'seriousNumAffected': 3}, {'id': 'EG003', 'title': 'Phase 1: RT+TMZ+HCQ - 800mg', 'description': 'Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday', 'otherNumAtRisk': 3, 'deathsNumAtRisk': 3, 'otherNumAffected': 3, 'seriousNumAtRisk': 3, 'deathsNumAffected': 0, 'seriousNumAffected': 3}, {'id': 'EG004', 'title': 'Phase 2: RT+TMZ+HCQ - MTD 600mg', 'description': 'Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg MTD. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday', 'otherNumAtRisk': 76, 'deathsNumAtRisk': 76, 'otherNumAffected': 76, 'seriousNumAtRisk': 76, 'deathsNumAffected': 0, 'seriousNumAffected': 53}], 'otherEvents': [{'term': 'abdominal distension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'mood alteration', 'notes': 'agitation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 14, 'numAffected': 14}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'alkaline phosphatase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'alopecia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'anemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 4, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 4, 'numAffected': 3}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 38, 'numAffected': 37}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'anorexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 15, 'numAffected': 15}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'anxiety', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'aspartate aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 11, 'numAffected': 11}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'ataxia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'bloating', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'blood bilirubin increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'bruising', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'blurred vision', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Eye disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'chills', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 12, 'numAffected': 12}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'creatinine increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'depression', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 14, 'numAffected': 14}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'dry skin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'dysarthria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'dysgeusia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'dyspepsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'dyspnea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'edema limbs', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'epistaxis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'erythema multiforme', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 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'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'stomach pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 13, 'numAffected': 13}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'weight loss', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'white blood cell count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 4, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 3, 'numAffected': 2}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 27, 'numAffected': 27}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}], 'seriousEvents': [{'term': 'abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'alkaline phosphatase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'anemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 4, 'numAffected': 3}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'anorexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'blood bilirubin increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'decreased depth perception', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Eye disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'febrile neutropenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'generalized muscle weakness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'hemolysis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'hyperkalemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'hyperuricemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'other', 'notes': 'strep bovis (sepsis)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'lymphocyte count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'neutrophil count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 3, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 10, 'numAffected': 8}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'rash maculo-papular', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 9, 'numAffected': 9}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'white blood cell count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 8, 'numAffected': 8}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}, {'term': 'platelet count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 3, 'numEvents': 4, 'numAffected': 3}, {'groupId': 'EG004', 'numAtRisk': 76, 'numEvents': 11, 'numAffected': 9}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE 3.0'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': '(Phase I) Maximum Tolerated Dose (MTD) of Hydroxychloroquine (HCQ)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 1 - Dose Finding', 'description': 'Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\ncohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.\n\ntemozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2\n\npharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)\n\nRadiation 6weeks during initation cycle Monday - Friday'}], 'classes': [{'title': '200mg', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}, {'title': '400mg', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}]}]}, {'title': '600mg', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}, {'title': '800mg', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '10 weeks', 'description': 'Number of participants who tolerated doses of HCQ without dose limiting toxicity. The highest dose at which participants did not experience dose limiting toxicity was determined as the MTD.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Cohort 200mg - 3 subjects ; cohort 400mg - 7 subjects; 600mg - 3 subjects; 800mg - 3 subjects'}, {'type': 'PRIMARY', 'title': '(Phase I) Number of Participants Who Experienced Dose Limiting Toxicity (DLT)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '3', 'groupId': 'OG002'}, {'value': '3', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 1: RT+TMZ+HCQ - 200mg', 'description': 'Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}, {'id': 'OG001', 'title': 'Phase 1: RT+TMZ+HCQ - 400mg', 'description': 'Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}, {'id': 'OG002', 'title': 'Phase 1: RT+TMZ+HCQ - 600mg', 'description': 'Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}, {'id': 'OG003', 'title': 'Phase 1: RT+TMZ+HCQ - 800mg', 'description': 'Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}, {'value': '3', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '10 weeks', 'description': 'Dose limiting toxicity defined as: Any DLT must be a toxicity considered at least possibly related to HCQ. DLTs will include any possibly, probably, or definitely HCQ-related Grade 3 or 4 toxicity. Known or reasonably suspected TMZ hematological toxicities will not be considered dose limiting unless the treating physician considers the toxicity to be exacerbated by HCQ. Nonhematological toxicities: Any Grades 3-4 severity (except nausea and vomiting without sufficient antiemetic prophylaxis)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': '1/7 subjects from the 400mg cohort only received 70% of expected dose, therefore this subject was not used for toxicity analysis'}, {'type': 'PRIMARY', 'title': '(Phase II) Overall Survival', 'denoms': [{'units': 'Participants', 'counts': [{'value': '76', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 2: RT + TMZ + HCQ', 'description': 'Daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nOther: pharmacological study (PK)\n\nPts will continue on treatment until tumor progression.\n\nPKs - correlatives will be collected in Phase 2\n\nRadiation (RT)\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}], 'classes': [{'categories': [{'measurements': [{'value': '15.6', 'groupId': 'OG000', 'lowerLimit': '13', 'upperLimit': '17'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '2 years', 'description': 'Number of months alive after end of study participation', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Only Phase 2 participants were assessed for this outcome measure.'}, {'type': 'SECONDARY', 'title': '(Phase II) Number of Participants With Grade 3 and 4 Toxicity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '76', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 2: RT + TMZ + HCQ', 'description': 'Daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nOther: pharmacological study (PK)\n\nPts will continue on treatment until tumor progression.\n\nPKs - correlatives will be collected in Phase 2\n\nRadiation (RT)\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}], 'classes': [{'categories': [{'measurements': [{'value': '22', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'up to 2 years', 'description': 'Number of participants experiencing Grade 3 and 4 toxicity, as defined by CTCAE v3.0, with a possible, probable or definite relationship to HCQ, TMZ or both', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Only participants from Phase II were assessed for this outcome measure.'}, {'type': 'SECONDARY', 'title': 'Pharmocodynamics as Determined by Number of Participants With Autophagy Inhibition', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 2: RT + TMZ + HCQ', 'description': 'Daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nOther: pharmacological study (PK)\n\nPts will continue on treatment until tumor progression.\n\nPKs - correlatives will be collected in Phase 2\n\nRadiation (RT)\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}], 'classes': [{'categories': [{'title': 'AV increase', 'measurements': [{'value': '22', 'groupId': 'OG000'}]}, {'title': 'No AV increase', 'measurements': [{'value': '18', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'up to 9 weeks', 'description': 'Number of participants with at least 2 peripheral blood mononuclear cell (PBMC) samples that were amenable to electronmicroscopy (EM) who showed an increase of autophagic vacuoles in cells.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Only 40 participants had at least 2 PBMC samples that were amenable to EM, which was required to assess this outcome measure.'}, {'type': 'SECONDARY', 'title': 'Pharmocodynamics as Determined by Number of Participants With Autophagy Inhibition in Relation to Maximal Concentration (Cmax) of HCQ', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'HCQ Cmax <= 1785 ng/mL', 'description': 'Participants from Phase I and II with a HCQ Cmax \\<= 1785 ng/mL\n\nCmax calculated based on 7 samples collected (baseline, initiation Cycle(C) W3-4, W9-10, Maintenance C1W4, C2W4, C3W4, C6W4)'}, {'id': 'OG001', 'title': 'HCQ Cmax>1785 ng/mL', 'description': 'Participants from Phase I and II with a HCQ Cmax\\>1785 ng/mL\n\nCmax calculated based on 7 samples collected (baseline, initiation Cycle(C) W3-4, W9-10, Maintenance C1W4, C2W4, C3W4, C6W4)'}], 'classes': [{'title': 'AV Increase', 'categories': [{'measurements': [{'value': '10', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}]}]}, {'title': 'No AV Increase', 'categories': [{'measurements': [{'value': '12', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'up to 9 weeks', 'description': 'Autophagy inhibition is represented by an increase in autophagic vacuoles (AV) in participants with at least 2 peripheral blood mononuclear cell samples that were amenable to EM.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Only participants who had at least 2 PBMC samples that were amenable to EM were assessed for this outcome measure'}, {'type': 'SECONDARY', 'title': 'Pharmacokinetics (PK) of Hydroxychloroquine as Measured by Lag Time (Tlag)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '72', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 2: RT + TMZ + HCQ', 'description': 'Daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nOther: pharmacological study (PK)\n\nPts will continue on treatment until tumor progression.\n\nPKs - correlatives will be collected in Phase 2\n\nRadiation (RT)\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}], 'classes': [{'categories': [{'measurements': [{'value': '1.06', 'groupId': 'OG000', 'lowerLimit': '0.97', 'upperLimit': '1.25'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 276 days', 'description': 'The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.', 'unitOfMeasure': 'hour', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Only participants from Phase II were assessed for this outcome measure. Data was not collected from 4/76 participants.'}, {'type': 'SECONDARY', 'title': 'PK of Hydroxychloroquine as Measured by Oral Clearance (Liters/Hour) From Central Compartment (CL/F)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '72', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 2: RT + TMZ + HCQ', 'description': 'Daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nOther: pharmacological study (PK)\n\nPts will continue on treatment until tumor progression.\n\nPKs - correlatives will be collected in Phase 2\n\nRadiation (RT)\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}], 'classes': [{'categories': [{'measurements': [{'value': '11.85', 'groupId': 'OG000', 'lowerLimit': '6.41', 'upperLimit': '28.18'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 276 days', 'description': 'The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.', 'unitOfMeasure': 'L/hr', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Only participants from Phase II were assessed for this outcome measure. Data was not collected from 4/76 participants.'}, {'type': 'SECONDARY', 'title': 'PK of Hydroxychloroquine as Measured by Volume of Distribution of Central Compartment (V/F)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '72', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 2: RT + TMZ + HCQ', 'description': 'Daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nOther: pharmacological study (PK)\n\nPts will continue on treatment until tumor progression.\n\nPKs - correlatives will be collected in Phase 2\n\nRadiation (RT)\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}], 'classes': [{'categories': [{'measurements': [{'value': '483.96', 'groupId': 'OG000', 'lowerLimit': '26', 'upperLimit': '5483'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 276 days', 'description': 'The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.', 'unitOfMeasure': 'Liters', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Only participants from Phase II were assessed for this outcome measure. Data was not collected from 4/76 participants.'}, {'type': 'SECONDARY', 'title': 'PK of Hydroxychloroquine as Measured by Distribution Volume of Peripheral Compartment (V2/F)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '72', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 2: RT + TMZ + HCQ', 'description': 'Daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nOther: pharmacological study (PK)\n\nPts will continue on treatment until tumor progression.\n\nPKs - correlatives will be collected in Phase 2\n\nRadiation (RT)\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}], 'classes': [{'categories': [{'measurements': [{'value': '963', 'groupId': 'OG000', 'lowerLimit': '558', 'upperLimit': '2208'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 276 days', 'description': 'The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.', 'unitOfMeasure': 'Liters', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Only participants from Phase II were assessed for this outcome measure. Data was not collected from 4/76 participants.'}, {'type': 'SECONDARY', 'title': 'PK of Hydroxychloroquine as Measured by First-order Absorption Rate Constant (Ka)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '72', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase 2: RT + TMZ + HCQ', 'description': 'Daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nOther: pharmacological study (PK)\n\nPts will continue on treatment until tumor progression.\n\nPKs - correlatives will be collected in Phase 2\n\nRadiation (RT)\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation: Radiation during the first six weeks of treatment Monday-Friday'}], 'classes': [{'categories': [{'measurements': [{'value': '0.51', 'groupId': 'OG000', 'lowerLimit': '0.42', 'upperLimit': '0.82'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 276 days', 'description': 'The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Only participants from Phase II were assessed for this outcome measure. Data was not collected from 4/76 participants.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'RT+TMZ+HCQ Phase 1 - 200 mg', 'description': 'Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nPhse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2\n\nhydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4'}, {'id': 'FG001', 'title': 'RT+TMZ+HCQ Phase 1 - 400 mg', 'description': 'Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 400mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nPhse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2\n\nhydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4'}, {'id': 'FG002', 'title': 'RT+TMZ+HCQ Phase 1 - 600 mg', 'description': 'Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 600mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nPhse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2\n\nhydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4'}, {'id': 'FG003', 'title': 'RT+TMZ+HCQ Phase 1 - 800 mg', 'description': 'Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 800mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nPhse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2\n\nhydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)\n\npharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4'}, {'id': 'FG004', 'title': 'RT+TMZ+HCQ Phase 2 - MTD 600 mg', 'description': 'Phse 2: daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 wks, 4 wkd of HCQ alone daily. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nPts will continue on treatment unitl tumor progression. PKs - correlatives will be collected in Phse 2\n\nRadiation'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '7'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '3'}, {'groupId': 'FG004', 'numSubjects': '76'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '6'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '3'}, {'groupId': 'FG004', 'numSubjects': '76'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}, {'type': 'Physician Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'This study was conducted by the Adult Brain Tumor Consortium (ABTC) and patients were recruited from the consortium members outpatient centers.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}, {'value': '76', 'groupId': 'BG001'}, {'value': '92', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'RT+TMZ+HCQ Phase 1', 'description': 'Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. then every 4 weeks will be cycle of mono therapy of HCQ daily.\n\ncohorts of three pts: dose levels: 200, 400, 600, 800mg. NO dose escalation beyond 800mg.\n\nhydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ TMZ days 1-5 150-20mg/m2 cycles 1-6\n\npharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation 6weeks during initiation cycle Monday - Friday'}, {'id': 'BG001', 'title': 'RT+TMZ+HCQ Phase 2', 'description': 'Daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and temozolomide for 6wks during RT. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\ntemozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ TMZ D1-5 150-20mg/m2 cycles 1-6\n\npharmacological study/Correlative study: Seven samples in total collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4\n\nRadiation 6weeks during initiation cycle Monday - Friday\n\nPts will continue on treatment unti/tumor progression.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '55', 'groupId': 'BG000', 'lowerLimit': '24', 'upperLimit': '69'}, {'value': '59', 'groupId': 'BG001', 'lowerLimit': '20', 'upperLimit': '83'}, {'value': '58', 'groupId': 'BG002', 'lowerLimit': '20', 'upperLimit': '83'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '30', 'groupId': 'BG001'}, {'value': '34', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '12', 'groupId': 'BG000'}, {'value': '46', 'groupId': 'BG001'}, {'value': '58', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Karnofsky Performance Status', 'classes': [{'title': '100', 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '15', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}]}]}, {'title': '90', 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '31', 'groupId': 'BG001'}, {'value': '38', 'groupId': 'BG002'}]}]}, {'title': '80', 'categories': [{'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '18', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}]}]}, {'title': '70', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '11', 'groupId': 'BG002'}]}]}, {'title': '60', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': "The Karnofsky Performance Score (KPS) measures individual's functional impairment to assess prognosis. Score ranges from 0-100 with a lower score reflecting a worse prognosis. KPS is categorized as follows: 0-40= Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly; 50-70= unable to work; able to live at home and care for most personal needs; varying amount of assistance needed; 80-100= able to carry on normal activity and to work; no special care needed. KPS \\>=60 is part of eligibility criteria for this study.", 'unitOfMeasure': 'Participants'}, {'title': 'Surgical Procedure', 'classes': [{'title': 'Biopsy', 'categories': [{'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '18', 'groupId': 'BG001'}, {'value': '24', 'groupId': 'BG002'}]}]}, {'title': 'Craniotomy', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '58', 'groupId': 'BG001'}, {'value': '68', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Baseline characteristics for all participants from Phase 1 were analyzed as a group.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 92}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-10-29'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-06', 'completionDateStruct': {'date': '2014-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-06-19', 'studyFirstSubmitDate': '2007-06-13', 'resultsFirstSubmitDate': '2019-05-09', 'studyFirstSubmitQcDate': '2007-06-13', 'lastUpdatePostDateStruct': {'date': '2019-07-10', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2019-06-19', 'studyFirstPostDateStruct': {'date': '2007-06-14', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-07-10', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2013-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '(Phase I) Maximum Tolerated Dose (MTD) of Hydroxychloroquine (HCQ)', 'timeFrame': '10 weeks', 'description': 'Number of participants who tolerated doses of HCQ without dose limiting toxicity. The highest dose at which participants did not experience dose limiting toxicity was determined as the MTD.'}, {'measure': '(Phase I) Number of Participants Who Experienced Dose Limiting Toxicity (DLT)', 'timeFrame': '10 weeks', 'description': 'Dose limiting toxicity defined as: Any DLT must be a toxicity considered at least possibly related to HCQ. DLTs will include any possibly, probably, or definitely HCQ-related Grade 3 or 4 toxicity. Known or reasonably suspected TMZ hematological toxicities will not be considered dose limiting unless the treating physician considers the toxicity to be exacerbated by HCQ. Nonhematological toxicities: Any Grades 3-4 severity (except nausea and vomiting without sufficient antiemetic prophylaxis)'}, {'measure': '(Phase II) Overall Survival', 'timeFrame': '2 years', 'description': 'Number of months alive after end of study participation'}], 'secondaryOutcomes': [{'measure': '(Phase II) Number of Participants With Grade 3 and 4 Toxicity', 'timeFrame': 'up to 2 years', 'description': 'Number of participants experiencing Grade 3 and 4 toxicity, as defined by CTCAE v3.0, with a possible, probable or definite relationship to HCQ, TMZ or both'}, {'measure': 'Pharmocodynamics as Determined by Number of Participants With Autophagy Inhibition', 'timeFrame': 'up to 9 weeks', 'description': 'Number of participants with at least 2 peripheral blood mononuclear cell (PBMC) samples that were amenable to electronmicroscopy (EM) who showed an increase of autophagic vacuoles in cells.'}, {'measure': 'Pharmocodynamics as Determined by Number of Participants With Autophagy Inhibition in Relation to Maximal Concentration (Cmax) of HCQ', 'timeFrame': 'up to 9 weeks', 'description': 'Autophagy inhibition is represented by an increase in autophagic vacuoles (AV) in participants with at least 2 peripheral blood mononuclear cell samples that were amenable to EM.'}, {'measure': 'Pharmacokinetics (PK) of Hydroxychloroquine as Measured by Lag Time (Tlag)', 'timeFrame': 'up to 276 days', 'description': 'The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.'}, {'measure': 'PK of Hydroxychloroquine as Measured by Oral Clearance (Liters/Hour) From Central Compartment (CL/F)', 'timeFrame': 'up to 276 days', 'description': 'The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.'}, {'measure': 'PK of Hydroxychloroquine as Measured by Volume of Distribution of Central Compartment (V/F)', 'timeFrame': 'up to 276 days', 'description': 'The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.'}, {'measure': 'PK of Hydroxychloroquine as Measured by Distribution Volume of Peripheral Compartment (V2/F)', 'timeFrame': 'up to 276 days', 'description': 'The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.'}, {'measure': 'PK of Hydroxychloroquine as Measured by First-order Absorption Rate Constant (Ka)', 'timeFrame': 'up to 276 days', 'description': 'The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['adult glioblastoma', 'adult gliosarcoma', 'adult giant cell glioblastoma'], 'conditions': ['Brain and Central Nervous System Tumors']}, 'referencesModule': {'references': [{'pmid': '24991840', 'type': 'RESULT', 'citation': "Rosenfeld MR, Ye X, Supko JG, Desideri S, Grossman SA, Brem S, Mikkelson T, Wang D, Chang YC, Hu J, McAfee Q, Fisher J, Troxel AB, Piao S, Heitjan DF, Tan KS, Pontiggia L, O'Dwyer PJ, Davis LE, Amaravadi RK. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy. 2014 Aug;10(8):1359-68. doi: 10.4161/auto.28984. Epub 2014 May 20."}]}, 'descriptionModule': {'briefSummary': 'RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving hydroxychloroquine together with temozolomide and radiation therapy may kill more tumor cells.\n\nPURPOSE: This phase I/II trial is studying the side effects and best dose of hydroxychloroquine when given together with radiation therapy and temozolomide and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme.', 'detailedDescription': 'OBJECTIVES:\n\nPrimary\n\n* Determine the maximum tolerated dose of hydroxychloroquine when administered in combination with radiotherapy and temozolomide in patients with newly diagnosed glioblastoma multiforme. (Phase I)\n* Assess the toxicity of this regimen in these patients. (Phase I)\n* Determine the overall survival of patients treated with this regimen. (Phase II)\n\nSecondary\n\n* Assess the frequency of toxicity of this regimen in these patients. (Phase II)\n* Evaluate the pharmacokinetics and pharmacodynamics of this regimen in these patients.\n* Correlate the average change in autophagic vesicles from baseline with genotype, toxicity, and clinical outcomes.\n* Correlate the presence of TP53 and PTEN genes and BECN1 with toxicity and clinical outcomes.\n\nOUTLINE: This is a multicenter, open-label, phase I, dose-escalation study of hydroxychloroquine followed by a phase II study.\n\n* Phase I:\n\n * Initiation therapy: Patients receive oral temozolomide daily for 6 weeks and undergo conformal or intensity-modulated radiotherapy 5 days a week for 6 weeks. Patients also receive oral hydroxychloroquine daily for 10 weeks beginning concurrently with temozolomide and radiotherapy.\n\nCohorts of 3-6 patients receive escalating doses of hydroxychloroquine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.\n\n* Maintenance therapy: Beginning 28 days after completion of radiotherapy, patients receive oral temozolomide on days 1-5 and oral hydroxychloroquine on days 1-28. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive hydroxychloroquine alone as above in the absence of disease progression or unacceptable toxicity.\n\n * Phase II:\n* Initiation therapy: Patients receive hydroxychloroquine at the MTD determined in phase I, temozolomide, and radiotherapy as in phase I.\n* Maintenance therapy: Patients receive hydroxychloroquine at the MTD determined in phase I and temozolomide as in phase I.\n\nPatients undergo blood and tissue sample collection periodically for pharmacological and correlative studies. Samples are analyzed for the mutational status of TP53 and PTEN genes and copy number of BECN1 via PCR; changes in autophagy protein LC3 via gel electrophoresis; and differences in the formation of LC3-II via immunoblotting.\n\nAfter completion of study treatment, patients are followed every 2 months.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '120 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'DISEASE CHARACTERISTICS:\n\n* Histologically confirmed grade IV supratentorial astrocytoma (glioblastoma multiforme)\n* Newly diagnosed disease\n* Diagnosis must have been made by biopsy or resection ≤ 3 months prior to study entry\n\nINCLUSION CRITERIA:\n\n* Patients must be at least 18 years of age.\n* Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme), established by biopsy or resection not more than 3 months prior to registration.\n* Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor. Glucocorticoid therapy is allowed.\n* Patients must have a Karnofsky performance status ≤ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others).\n* Patients must have the following hematologic, renal and liver function (i.e. absolute neutrophil count \\> 1500/mm3, platelets \\> 100,000/mm3, creatinine ≤ 2 times the upper limits of normal (ULN) total bilirubin ≤ 1.5 mg/dl, ALT and AST ≤ 4 times above the upper limits of the institutional norm.\n* Patients must be able to provide written informed consent.\n* Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant.\n* Patients must have a Mini Mental State Exam (MMSE) score of \\> 15.\n* Patients must have tumor tissue form completed and signed by a pathologist. See section 9.5.2 for details.\n* Prior concurrent therapy:\n\n * No prior radiotherapy, chemotherapy, immunotherapy, biologic agents (e.g., immunotoxins, immunoconjugates, antisense agents, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cell therapy, or gene therapy), or hormonal therapy for brain tumor\n * No prior polifeprosan 20 with carmustine implant (Gliadel wafer) or GliaSite® brachytherapy\n * No concurrent cytochrome P450 enzyme-inducing anticonvulsant drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, or oxcarbazepine)\n * No other concurrent chemotherapeutic or investigational agents for this cancer\n * Concurrent glucocorticoids allowed\n\nEXCLUSION CRITERIA:\n\n* Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.\n* Patients who are pregnant or breast-feeding.\n* Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents).\n* Patients with a concurrent or prior malignancy, unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for five years are eligible for this study.\n* Patients who have received Gliadel wafers or GliaSite brachytherapy are not eligible.\n* Due to risk of disease exacerbation patients with porphyria are not eligible.\n* Due to risk of disease exacerbation patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations.\n* Patients receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (EIADs) (i.e. phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine).\n* Patients with previously documented macular degeneration or diabetic retinopathy.'}, 'identificationModule': {'nctId': 'NCT00486603', 'briefTitle': 'Hydroxychloroquine, Radiation, and Temozolomide Treating Patients With Newly Diagnosed Glioblastoma Multiforme', 'organization': {'class': 'OTHER', 'fullName': 'Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins'}, 'officialTitle': 'A Phase I/II Trial of Hydroxychloroquine in Conjunction With Radiation Therapy and Concurrent and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme', 'orgStudyIdInfo': {'id': 'NABTT-0603'}, 'secondaryIdInfos': [{'id': 'U01CA062475', 'link': 'https://reporter.nih.gov/quickSearch/U01CA062475', 'type': 'NIH'}, {'id': 'ABTC-0603', 'type': 'OTHER', 'domain': 'Adult Brain Tumor Consortium'}, {'id': 'CDR0000549734', 'type': 'OTHER', 'domain': 'NCI PDQ'}, {'id': 'NA_00012420', 'type': 'OTHER', 'domain': 'JHM IRB'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Phase 1: RT+TMZ+HCQ 200 mg', 'description': 'Phse I: daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\ncohorts of three pts: dose levels: 200, 400, 800mg. NO dose escalation beyond 800mg.\n\nOther: pharmacological study (PK)\n\npts continue on treatment until tumor progression. PKs - correlatives will be collected in Phase 1\n\nRadiation (RT)', 'interventionNames': ['Drug: hydroxychloroquine', 'Drug: temozolomide', 'Other: pharmacological study', 'Radiation: Radiation']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1: RT+TMZ+HCQ 400 mg', 'description': 'Phse I: daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT, 400 mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\ncohorts of three pts: dose levels: 200, 400, 800mg. NO dose escalation beyond 800mg.\n\nOther: pharmacological study (PK)\n\npts continue on treatment until tumor progression. PKs - correlatives will be collected in Phase 1\n\nRadiation (RT)', 'interventionNames': ['Drug: hydroxychloroquine', 'Drug: temozolomide', 'Other: pharmacological study', 'Radiation: Radiation']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1: RT+TMZ+HCQ 600 mg', 'description': 'Phse I: daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT, 600 mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\ncohorts of three pts: dose levels: 200, 400, 800mg. NO dose escalation beyond 800mg.\n\nOther: pharmacological study (PK)\n\npts continue on treatment until tumor progression. PKs - correlatives will be collected in Phase 1\n\nRadiation (RT)', 'interventionNames': ['Drug: hydroxychloroquine', 'Drug: temozolomide', 'Other: pharmacological study', 'Radiation: Radiation']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1: RT+TMZ+HCQ 800 mg', 'description': 'Phse I: daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT, 800 mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\ncohorts of three pts: dose levels: 200, 400, 800mg. NO dose escalation beyond 800mg.\n\nOther: pharmacological study (PK)\n\npts continue on treatment until tumor progression. PKs - correlatives will be collected in Phase 1\n\nRadiation (RT)', 'interventionNames': ['Drug: hydroxychloroquine', 'Drug: temozolomide', 'Other: pharmacological study', 'Radiation: Radiation']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 2: RT + TMZ + HCQ MTD', 'description': 'Phse 2: daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 weeks, 4 weeks of HCQ alone daily. Complete 10 week cycle -Initiation Phase\n\nMaintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.\n\nOther: pharmacological study (PK)\n\nPts will continue on treatment until tumor progression. PKs - correlatives will be collected in Phase 2\n\nRadiation (RT)', 'interventionNames': ['Drug: hydroxychloroquine', 'Drug: temozolomide', 'Other: pharmacological study', 'Radiation: Radiation']}], 'interventions': [{'name': 'hydroxychloroquine', 'type': 'DRUG', 'otherNames': ['Plaquenil', 'HCQ'], 'description': 'see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles', 'armGroupLabels': ['Phase 1: RT+TMZ+HCQ 200 mg', 'Phase 1: RT+TMZ+HCQ 400 mg', 'Phase 1: RT+TMZ+HCQ 600 mg', 'Phase 1: RT+TMZ+HCQ 800 mg', 'Phase 2: RT + TMZ + HCQ MTD']}, {'name': 'temozolomide', 'type': 'DRUG', 'otherNames': ['Temodar', 'TMZ'], 'description': 'TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)', 'armGroupLabels': ['Phase 1: RT+TMZ+HCQ 200 mg', 'Phase 1: RT+TMZ+HCQ 400 mg', 'Phase 1: RT+TMZ+HCQ 600 mg', 'Phase 1: RT+TMZ+HCQ 800 mg', 'Phase 2: RT + TMZ + HCQ MTD']}, {'name': 'pharmacological study', 'type': 'OTHER', 'otherNames': ['PK', 'correlative studies'], 'description': 'Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4', 'armGroupLabels': ['Phase 1: RT+TMZ+HCQ 200 mg', 'Phase 1: RT+TMZ+HCQ 400 mg', 'Phase 1: RT+TMZ+HCQ 600 mg', 'Phase 1: RT+TMZ+HCQ 800 mg', 'Phase 2: RT + TMZ + HCQ MTD']}, {'name': 'Radiation', 'type': 'RADIATION', 'otherNames': ['RT'], 'description': 'Radiation during the first six weeks of treatment Monday-Friday', 'armGroupLabels': ['Phase 1: RT+TMZ+HCQ 200 mg', 'Phase 1: RT+TMZ+HCQ 400 mg', 'Phase 1: RT+TMZ+HCQ 600 mg', 'Phase 1: RT+TMZ+HCQ 800 mg', 'Phase 2: RT + TMZ + HCQ MTD']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35294', 'city': 'Birmingham', 'state': 'Alabama', 'country': 'United States', 'facility': 'University of Alabama at Birmingham Comprehensive Cancer Center', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '33612-9497', 'city': 'Tampa', 'state': 'Florida', 'country': 'United States', 'facility': 'H. Lee Moffitt Cancer Center and Research Institute at University of South Florida', 'geoPoint': {'lat': 27.94752, 'lon': -82.45843}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Winship Cancer Institute of Emory University', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '21231-2410', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '02114', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Massachusetts General Hospital', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '48202', 'city': 'Detroit', 'state': 'Michigan', 'country': 'United States', 'facility': 'Josephine Ford Cancer Center at Henry Ford Hospital', 'geoPoint': {'lat': 42.33143, 'lon': -83.04575}}, {'zip': '27157-1096', 'city': 'Winston-Salem', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Wake Forest University Comprehensive Cancer Center', 'geoPoint': {'lat': 36.09986, 'lon': -80.24422}}, {'zip': '44106-5065', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'Case Comprehensive Cancer Center', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'zip': '19104-4283', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'Abramson Cancer Center of the University of Pennsylvania', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}], 'overallOfficials': [{'name': 'Myrna Rosenfeld, MD, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'New Approaches to Brain Tumor Therapy/Adult Brain Tumor Consortium'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR'}}}}