Ignite Creation Date:
2025-12-24 @ 4:18 PM
Ignite Modification Date:
2025-12-25 @ 7:01 PM
Study NCT ID:
NCT00605566
Status:
COMPLETED
Last Update Posted:
2019-02-19
First Post:
2008-01-18
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018358', 'term': 'Neuroendocrine Tumors'}], 'ancestors': [{'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077157', 'term': 'Sorafenib'}, {'id': 'D003520', 'term': 'Cyclophosphamide'}], 'ancestors': [{'id': 'D010671', 'term': 'Phenylurea Compounds'}, {'id': 'D014508', 'term': 'Urea'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009536', 'term': 'Niacinamide'}, {'id': 'D009539', 'term': 'Nicotinic Acids'}, {'id': 'D000147', 'term': 'Acids, Heterocyclic'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011725', 'term': 'Pyridines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D010752', 'term': 'Phosphoramide Mustards'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'lillian.siu@uhn.ca', 'title': 'Dr. Lillian Siu', 'organization': 'Princess Margaret Cancer Centre'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Adverse event data were collected over a total of 160 treatment cycles (1 cycle = 28 days) for all study participants, for as long as 7 years.', 'eventGroups': [{'id': 'EG000', 'title': 'Sorafenib Plus Cyclophosphamide', 'description': 'Patients will receive sorafenib and cyclophosphamide.\n\nsorafenib and cyclophosphamide: During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \\> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.', 'otherNumAtRisk': 22, 'otherNumAffected': 22, 'seriousNumAtRisk': 22, 'seriousNumAffected': 11}], 'otherEvents': [{'term': 'Palmar-plantar erythrodysesthesia syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 10}], 'organSystem': 'Skin and subcutaneous tissue disorders'}, {'term': 'Dysgeusia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 5}], 'organSystem': 'Nervous system disorders'}, {'term': 'Hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 3}], 'organSystem': 'Vascular disorders'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 9}], 'organSystem': 'General disorders'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 12}], 'organSystem': 'Gastrointestinal disorders'}, {'term': 'Alopecia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 4}], 'organSystem': 'Skin and subcutaneous tissue disorders'}, {'term': 'Hypophosphatemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 11}], 'organSystem': 'Metabolism and nutrition disorders'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 9}], 'organSystem': 'Skin and subcutaneous tissue disorders'}, {'term': 'Lymphopenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 7}], 'organSystem': 'Investigations'}, {'term': 'Weight loss', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 6}], 'organSystem': 'Investigations'}, {'term': 'Aspartate aminotransferase elevation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 6}], 'organSystem': 'Investigations'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 8}], 'organSystem': 'Gastrointestinal disorders'}, {'term': 'Thrombocytopenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 3}], 'organSystem': 'Investigations'}, {'term': 'Lipase elevation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 6}], 'organSystem': 'Investigations'}, {'term': 'Peripheral sensory neuropathy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 1}], 'organSystem': 'Nervous system disorders'}, {'term': 'Amylase elevation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 5}], 'organSystem': 'Investigations'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders'}, {'term': 'Alanine aminotransferase elevation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 3}], 'organSystem': 'Investigations'}, {'term': 'Hypocalcemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numAffected': 3}], 'organSystem': 'Metabolism and nutrition disorders'}], 'seriousEvents': [{'term': 'Ileal perforation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders'}, {'term': 'Abdominal Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders'}, {'term': 'Flushing', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders'}, {'term': 'Palmar-plantar erythrodysesthesia syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders'}, {'term': 'Protein Urine Positive', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders'}, {'term': 'Dyspepsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders'}, {'term': 'Weight Gain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations'}, {'term': 'Disease progression', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'Bilirubin increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations'}, {'term': 'Lipase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Investigations'}, {'term': 'Amylase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations'}, {'term': 'Fever', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders'}, {'term': 'Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations'}, {'term': 'Neck pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders'}, {'term': 'Small intestinal obstruction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Efficacy of Combination Sorafenib Plus Metronomic Cyclophosphamide in Advanced, Progressive NET, as Measured by the Objective Response Rate (ORR).', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sorafenib and Cyclophosphamide', 'description': 'Patients will receive sorafenib and cyclophosphamide.\n\nsorafenib and cyclophosphamide: During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \\> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years', 'description': 'Objective response (complete and partial) evaluated using RECIST criteria. Complete response (CR): disappearance of all clinical and radiological evidence of tumour (both target and non-target).\n\nPartial response (PR): at least a 30% decrease in the sum of longest diameter of target lesions.', 'calculatePct': False, 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': '19 out of 22 patients were evaluable for response.'}, {'type': 'PRIMARY', 'title': 'Association Between p-Shift Changes and Treatment Efficacy of Individual Dose Adjustment of Sorafenib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sorafenib and Cyclophosphamide', 'description': 'Patients will receive sorafenib and cyclophosphamide.\n\nsorafenib and cyclophosphamide: During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \\> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.'}], 'classes': [{'title': 'PFS in patients with a negative pShift result', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '2.8', 'groupId': 'OG000', 'lowerLimit': '1.8', 'upperLimit': '6.7'}]}]}, {'title': 'PFS in patients with a positive pShift result', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '14.9', 'comment': 'Not reached', 'groupId': 'OG000', 'lowerLimit': '3', 'upperLimit': 'NA'}]}]}, {'title': 'OS for patients with a negative pShift', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '6.4', 'groupId': 'OG000', 'lowerLimit': '2.8', 'upperLimit': '6.4'}]}]}, {'title': 'OS for patients with a positive pShift', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '21.3', 'comment': 'Not reached', 'groupId': 'OG000', 'lowerLimit': '7.9', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Assessed from start of study treatment until death, assessed up to 7 years.', 'description': 'A phosphoshift (pShift) flow cytometry-based test that measures RAF signal transduction capacity in peripheral blood cells was used in order to predict clinical course and/or guide individual dose-titration. Positive pShift values denote stimulation of RAF signal transduction, whereas negative pShift values denote inhibition of RAF signal transduction as measured by flow-cytometry.\n\nAssociations between pShift changes and treatment efficacy were measured using progression-free survival (PFS) and overall survival (OS).', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': '6 patients experienced a pharmacodynamic pShift change that was classified as positive, 16 experienced a negative pShift.'}, {'type': 'SECONDARY', 'title': 'Progression-free Survival (PFS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sorafenib and Cyclophosphamide', 'description': 'Patients will receive sorafenib and cyclophosphamide.\n\nsorafenib and cyclophosphamide: During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \\> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000', 'lowerLimit': '2', 'upperLimit': '10.7'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years', 'description': 'Progressive disease (PD): at least a 20% increase in the sum of the longest diameter of measured lesions.', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Overall Survival (OS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sorafenib and Cyclophosphamide', 'description': 'Patients will receive sorafenib and cyclophosphamide.\n\nsorafenib and cyclophosphamide: During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \\> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.'}], 'classes': [{'categories': [{'measurements': [{'value': '11.7', 'comment': 'Not reached', 'groupId': 'OG000', 'lowerLimit': '4.3', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Assessed from start of study treatment until death, assessed up to 7 years.', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': '1-year Survival Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sorafenib and Cyclophosphamide', 'description': 'Patients will receive sorafenib and cyclophosphamide.\n\nsorafenib and cyclophosphamide: During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \\> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.'}], 'classes': [{'categories': [{'measurements': [{'value': '45', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '1 year', 'description': 'Survival rate at 1 year.', 'unitOfMeasure': 'percentage of participants', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Sorafenib and Cyclophosphamide', 'description': 'Patients will receive sorafenib and cyclophosphamide.\n\nsorafenib and cyclophosphamide: During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \\> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '22'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Clinical deterioration', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Poor compliance in run-in period', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'Patients were recruited from January 2008 to October 2010.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Sorafenib Plus Cyclophosphamide', 'description': 'Patients will receive sorafenib and cyclophosphamide.\n\nsorafenib and cyclophosphamide: During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \\> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '17', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '58', 'groupId': 'BG000', 'lowerLimit': '32', 'upperLimit': '80'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '12', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'SUPPORTIVE_CARE', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 22}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2008-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-10', 'completionDateStruct': {'date': '2015-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-10-09', 'studyFirstSubmitDate': '2008-01-18', 'resultsFirstSubmitDate': '2017-10-30', 'studyFirstSubmitQcDate': '2008-01-18', 'lastUpdatePostDateStruct': {'date': '2019-02-19', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-10-09', 'studyFirstPostDateStruct': {'date': '2008-01-31', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-02-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2015-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Efficacy of Combination Sorafenib Plus Metronomic Cyclophosphamide in Advanced, Progressive NET, as Measured by the Objective Response Rate (ORR).', 'timeFrame': 'Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years', 'description': 'Objective response (complete and partial) evaluated using RECIST criteria. Complete response (CR): disappearance of all clinical and radiological evidence of tumour (both target and non-target).\n\nPartial response (PR): at least a 30% decrease in the sum of longest diameter of target lesions.'}, {'measure': 'Association Between p-Shift Changes and Treatment Efficacy of Individual Dose Adjustment of Sorafenib', 'timeFrame': 'Assessed from start of study treatment until death, assessed up to 7 years.', 'description': 'A phosphoshift (pShift) flow cytometry-based test that measures RAF signal transduction capacity in peripheral blood cells was used in order to predict clinical course and/or guide individual dose-titration. Positive pShift values denote stimulation of RAF signal transduction, whereas negative pShift values denote inhibition of RAF signal transduction as measured by flow-cytometry.\n\nAssociations between pShift changes and treatment efficacy were measured using progression-free survival (PFS) and overall survival (OS).'}], 'secondaryOutcomes': [{'measure': 'Progression-free Survival (PFS)', 'timeFrame': 'Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years', 'description': 'Progressive disease (PD): at least a 20% increase in the sum of the longest diameter of measured lesions.'}, {'measure': 'Overall Survival (OS)', 'timeFrame': 'Assessed from start of study treatment until death, assessed up to 7 years.'}, {'measure': '1-year Survival Rate', 'timeFrame': '1 year', 'description': 'Survival rate at 1 year.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Neuroendocrine', 'sorafenib', 'cyclophosphamide', 'pharmacodynamic'], 'conditions': ['Neuroendocrine Tumors']}, 'descriptionModule': {'briefSummary': "This is a phase II clinical trial to assess the efficacy of the combination of metronomic cyclophosphamide and tailored sorafenib dosing in advanced, progressive NET. NET are highly vascular tumors, and high VEGF expression has been correlated with worse clinical and pathological characteristics as well as poor prognosis. A novel antiangiogenic approach relies on targeting not only the endothelial cells but also rendering them more sensitive to VEGFR blockade by achieving pericyte detachment. In this study, the dose of sorafenib will be titrated up to a maximum of 800mg BID based on patients' toxicity and on a novel pharmacodynamic assay that measures inhibition of molecular target(PDGFR) in patients' peripheral blood mononuclear cells. Dual VEGFR targeting is achieved by administering sorafenib plus metronomic low dose cyclophosphamide."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Histologically or cytologically confirmed neuroendocrine tumors\n* Progressive and measurable metastatic disease\n* Patients must not have disease that is currently amenable to surgery\n* Life expectancy of greater than 3 months\n* ECOG performance status ≤2\n* Patients must have normal organ and marrow function\n* Negative pregnancy test; agreement to use adequate birth control\n\nExclusion Criteria:\n\n* Patients receiving chemotherapy or radiotherapy within last 4 weeks\n* Patients that had received Sorafenib for advanced NET(neuroendocrine tumors) are not allowed\n* Any other investigational agents within 4 weeks of study\n* Patients with known brain metastases\n* History of allergic reactions to compounds of similar chemical/biologic composition to sorafenib or cyclophosphamide\n* Concurrent cancer from another primary site requiring treatment within the past 3 years\n* Uncontrolled intercurrent illness\n* Pregnant women and women who are breastfeeding\n* HIV-positive patients receiving combination anti-retroviral therapy'}, 'identificationModule': {'nctId': 'NCT00605566', 'briefTitle': 'Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors', 'organization': {'class': 'OTHER', 'fullName': 'University Health Network, Toronto'}, 'officialTitle': 'Tailored-dose Sorafenib Plus Metronomic Cyclophosphamide in Advanced Neuroendocrine Tumors (NET): a Phase II Clinical Trial Based on Individual Pharmacodynamic Assessment', 'orgStudyIdInfo': {'id': 'SOR-NET-001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'I', 'description': 'Patients will receive sorafenib and cyclophosphamide.', 'interventionNames': ['Drug: Sorafenib', 'Drug: Cyclophosphamide']}], 'interventions': [{'name': 'Sorafenib', 'type': 'DRUG', 'otherNames': ['BAY 43-9006'], 'description': 'During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \\> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.', 'armGroupLabels': ['I']}, {'name': 'Cyclophosphamide', 'type': 'DRUG', 'otherNames': ['Cytoxan'], 'description': 'During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of \\> 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.', 'armGroupLabels': ['I']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'M5G 2M9', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Princess Margaret Hospital', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}], 'overallOfficials': [{'name': 'Lillian Siu, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Health Network, Toronto'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Health Network, Toronto', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}