Ignite Creation Date:
2025-12-24 @ 9:42 PM
Ignite Modification Date:
2026-02-22 @ 10:14 AM
Study NCT ID:
NCT00553332
Status:
COMPLETED
Last Update Posted:
2016-04-22
First Post:
2007-11-02
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Selumetinib in Treating Patients With Biliary Cancer That Cannot Be Removed By Surgery
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006528', 'term': 'Carcinoma, Hepatocellular'}, {'id': 'D001650', 'term': 'Bile Duct Neoplasms'}], 'ancestors': [{'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008113', 'term': 'Liver Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D001661', 'term': 'Biliary Tract Neoplasms'}, {'id': 'D001649', 'term': 'Bile Duct Diseases'}, {'id': 'D001660', 'term': 'Biliary Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C517975', 'term': 'AZD 6244'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'Tanios.Bekaii-Saab@osumc.edu', 'phone': '614-293-9863', 'title': 'Tanios Bekaii-Saab, MD', 'organization': 'The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute'}, 'certainAgreement': {'restrictionType': 'LTE60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'All patients were evaluated for toxicity using the NCI Common Toxicity Criteria version 3.0 from the time of their first treatment until the end of treatment.', 'eventGroups': [{'id': 'EG000', 'title': 'Treatment (Enzyme Inhibitor Therapy)', 'description': 'Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nselumetinib: Given orally\n\nlaboratory biomarker analysis: Correlative studies', 'otherNumAtRisk': 28, 'otherNumAffected': 28, 'seriousNumAtRisk': 28, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 25, 'numAffected': 25}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Xerostomia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 15, 'numAffected': 15}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 14, 'numAffected': 14}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 14, 'numAffected': 14}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 13, 'numAffected': 13}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Bloating', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 12, 'numAffected': 12}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Dry Skin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 11, 'numAffected': 11}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Dysgeusia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 8, 'numAffected': 8}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Mucositis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 7, 'numAffected': 7}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Flatulence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Thrombocytopenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Pruritus', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Alopecia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}, {'term': 'Hypokalemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE version 3.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Objective Response Rate (CR and PR)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '25', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment (Enzyme Inhibitor Therapy)', 'description': 'Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nselumetinib: Given orally\n\nlaboratory biomarker analysis: Correlative studies'}], 'classes': [{'title': 'Complete Response', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Partial Response', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Every 8 weeks', 'description': 'Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \\>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR', 'unitOfMeasure': 'patients', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Toxicity Profile of AZD6244', 'denoms': [{'units': 'Participants', 'counts': [{'value': '28', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment (Enzyme Inhibitor Therapy)', 'description': 'Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nselumetinib: Given orally\n\nlaboratory biomarker analysis: Correlative studies'}], 'classes': [{'title': 'Rash', 'categories': [{'measurements': [{'value': '90', 'groupId': 'OG000'}]}]}, {'title': 'Xerostomia', 'categories': [{'measurements': [{'value': '54', 'groupId': 'OG000'}]}]}, {'title': 'Nausea', 'categories': [{'measurements': [{'value': '50', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From the time of first treatment with AZD6244, assessed up to 4 weeks', 'description': 'Toxicitity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0', 'unitOfMeasure': 'percent of patients', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Median Progression Free Survival for Patients', 'denoms': [{'units': 'Participants', 'counts': [{'value': '28', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment (Enzyme Inhibitor Therapy)', 'description': 'Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nselumetinib: Given orally\n\nlaboratory biomarker analysis: Correlative studies'}], 'classes': [{'categories': [{'measurements': [{'value': '3.7', 'groupId': 'OG000', 'lowerLimit': '3.5', 'upperLimit': '4.9'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Up to 6 months', 'description': 'Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Overall Survival', 'denoms': [{'units': 'Participants', 'counts': [{'value': '28', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment (Enzyme Inhibitor Therapy)', 'description': 'Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nselumetinib: Given orally\n\nlaboratory biomarker analysis: Correlative studies'}], 'classes': [{'categories': [{'measurements': [{'value': '9.8', 'comment': 'Too early to reach the upper 95% confidence interval', 'groupId': 'OG000', 'lowerLimit': '3.50', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Up to 12 months', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Kaplan-Meier'}, {'type': 'SECONDARY', 'title': 'RAS/RAF/MEK/ERK Signaling Pathway Activation', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment (Enzyme Inhibitor Therapy)', 'description': 'Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nselumetinib: Given orally\n\nlaboratory biomarker analysis: Correlative studies'}], 'timeFrame': 'At baseline', 'reportingStatus': 'POSTED', 'populationDescription': 'Data was not collected and analyzed'}, {'type': 'SECONDARY', 'title': 'Protein Levels of RAS/RAF/MEK/ERK Signaling Pathway Activation', 'denoms': [{'units': 'Participants', 'counts': [{'value': '28', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment (Enzyme Inhibitor Therapy)', 'description': 'Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nselumetinib: Given orally\n\nlaboratory biomarker analysis: Correlative studies'}], 'classes': [{'title': 'pAKT', 'categories': [{'measurements': [{'value': '1.23', 'spread': '0.98', 'groupId': 'OG000'}]}]}, {'title': 'pERK', 'categories': [{'measurements': [{'value': '1.36', 'spread': '1.09', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At baseline', 'description': 'Measure the proteins levels of RAS/RAF/MEK/ERK signaling pathway activation to AZD6244', 'unitOfMeasure': 'mg/ml', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Only 27 patients had pAKT and pERK performed due to 2 samples not available for analysis'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Treatment (Enzyme Inhibitor Therapy)', 'description': 'Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nselumetinib: Given orally\n\nlaboratory biomarker analysis: Correlative studies'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '29'}]}, {'type': 'COMPLETED', 'achievements': [{'comment': 'evaluable for response', 'groupId': 'FG000', 'numSubjects': '28'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'ineligible, incorrect diagnosis', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'Patients were enrolled to the trial between December 2007 and January 2009'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '28', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Treatment (Enzyme Inhibitor Therapy)', 'description': 'Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nselumetinib: Given orally\n\nlaboratory biomarker analysis: Correlative studies'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '55.6', 'groupId': 'BG000', 'lowerLimit': '26', 'upperLimit': '79'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '9', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '19', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '27', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '28', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'patients'}, {'title': 'Eastern Cooperative Oncology Group (ECOG)', 'classes': [{'title': '0 (Fully active)', 'categories': [{'measurements': [{'value': '11', 'groupId': 'BG000'}]}]}, {'title': '1 (Restricted activity)', 'categories': [{'measurements': [{'value': '17', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'patients'}, {'title': 'Disease site', 'classes': [{'title': 'Intrahepatic', 'categories': [{'measurements': [{'value': '17', 'groupId': 'BG000'}]}]}, {'title': 'Gallbladder', 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}]}]}, {'title': 'Extrahepatic', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'patients'}, {'title': 'Metastasis site', 'classes': [{'title': 'Liver only', 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}]}]}, {'title': 'Liver and other sites', 'categories': [{'measurements': [{'value': '16', 'groupId': 'BG000'}]}]}, {'title': 'Other (soft tissue, lymph nodes and lung)', 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'patients'}, {'title': 'Number of target lesions', 'classes': [{'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000', 'lowerLimit': '1', 'upperLimit': '13'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'lesions', 'dispersionType': 'FULL_RANGE'}], 'populationDescription': 'All patients had metastatic disease.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 29}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-03', 'completionDateStruct': {'date': '2013-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-03-22', 'studyFirstSubmitDate': '2007-11-02', 'resultsFirstSubmitDate': '2015-09-11', 'studyFirstSubmitQcDate': '2007-11-02', 'lastUpdatePostDateStruct': {'date': '2016-04-22', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2016-03-22', 'studyFirstPostDateStruct': {'date': '2007-11-05', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2016-04-22', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Objective Response Rate (CR and PR)', 'timeFrame': 'Every 8 weeks', 'description': 'Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \\>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR'}], 'secondaryOutcomes': [{'measure': 'Toxicity Profile of AZD6244', 'timeFrame': 'From the time of first treatment with AZD6244, assessed up to 4 weeks', 'description': 'Toxicitity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0'}, {'measure': 'Median Progression Free Survival for Patients', 'timeFrame': 'Up to 6 months', 'description': 'Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions'}, {'measure': 'Overall Survival', 'timeFrame': 'Up to 12 months'}, {'measure': 'RAS/RAF/MEK/ERK Signaling Pathway Activation', 'timeFrame': 'At baseline'}, {'measure': 'Protein Levels of RAS/RAF/MEK/ERK Signaling Pathway Activation', 'timeFrame': 'At baseline', 'description': 'Measure the proteins levels of RAS/RAF/MEK/ERK signaling pathway activation to AZD6244'}]}, 'conditionsModule': {'conditions': ['Liver and Intrahepatic Biliary Tract Cancer', 'Recurrent Extrahepatic Bile Duct Cancer', 'Unresectable Extrahepatic Bile Duct Cancer']}, 'referencesModule': {'references': [{'pmid': '21519026', 'type': 'RESULT', 'citation': "Bekaii-Saab T, Phelps MA, Li X, Saji M, Goff L, Kauh JS, O'Neil BH, Balsom S, Balint C, Liersemann R, Vasko VV, Bloomston M, Marsh W, Doyle LA, Ellison G, Grever M, Ringel MD, Villalona-Calero MA. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol. 2011 Jun 10;29(17):2357-63. doi: 10.1200/JCO.2010.33.9473. Epub 2011 Apr 25."}]}, 'descriptionModule': {'briefSummary': 'This phase II trial is studying how well selumetinib works in treating patients with biliary cancer that cannot be removed by surgery. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.', 'detailedDescription': 'PRIMARY OBJECTIVES:\n\nI. To evaluate the objective response rate (complete response \\[CR\\] and partial response \\[PR\\]) in patients with unresectable biliary carcinoma treated with AZD6244 (selumetinib).\n\nSECONDARY OBJECTIVES:\n\nI. To evaluate the toxicity profile of this drug in these patients. II. To evaluate the 6- and 12-month survival, 6-month progression-free survival, and overall survival rates of patients treated with this drug.\n\nIII. To correlate genetic mutations, epigenetic silencing, and/or protein levels of RAS/RAF/MEK/ERK signaling pathway activation with therapeutic efficacy of AZD6244 in these patients.\n\nIV. To genotype tumors for the presence of RAS mutations (i.e., NRAS, KRAS, HRAS) and BRAF mutations (e.g., V600E) in biliary tumor samples from these patients.\n\nV. To assess the presence of activation of the MEK1, MEK2, ERK, and/or Akt pathways in tumor samples from these patients.\n\nVI. To assess the epigenetic alterations (i.e., methylation) affecting the level of gene/protein expression of RASSF1A, NORE1A, and NORE1B in tumor samples from these patients.\n\nOUTLINE:\n\nPatients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nFormalin fixed paraffin-embedded tissue blocks or fresh tissue samples are obtained from all patients prior to treatment. Tissue samples are analyzed by immunohistochemistry for the expression level of target proteins (MEK, p-MEK, ERK, p-ERK, Akt, p-AKT, RASSF1A, NORE1A and NORE1B); PCR for mutational status of target genes RAS, BRAF and EGFR); and in methylation-specific PCR for methylation of target gene promoters (promoters for RASSF1A, NORE1A and NORE1B). Samples are also analyzed by quantitative real-time PCR to compare methylation status. Fresh frozen tissue, when available, is evaluated by Western analysis to measure expression levels of target proteins.\n\nAfter completion of study treatment, patients are followed up for 4 weeks.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Histologically confirmed biliary tract carcinoma\n\n * Surgically unresectable disease\n* Meets any of the following criteria for biliary cancers only:\n\n * Received ≤ 1 prior systemic anticancer therapy, including chemoembolization\n * Received prior cryotherapy, radiofrequency ablation, ethanol injection, transarterial chemoembolization, or photodynamic therapy AND meets the following criteria:\n\n * More than 6 weeks have elapsed since any of the prior therapy described above\n * Indicator lesion(s) must be outside the area of prior treatment OR must demonstrate clear evidence of disease progression if the only indicator lesion is inside the prior treatment area\n * Indicator lesion must have clearly distinct edges on CT scan\n * Prior radiotherapy with or without the use of a fluoropyrimidine as a radiosensitizer is allowed, provided more than 12 weeks have elapsed since treatment\n* Fresh or paraffin-embedded tissue from tumor blocks must be available for review\n* Measurable disease, defined as ≥ 1 unidimensionally measurable lesion \\> 20 mm by conventional techniques or \\> 10 mm by spiral CT scan\n* No known brain metastases\n* Life expectancy \\> 12 weeks\n* ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%\n* ANC ≥ 1,500/μL\n* Platelet count ≥ 75,000/μL\n* Total bilirubin ≤ 2 times upper limit of normal(ULN)\n* AST or ALT ≤ 3 times ULN\n* Serum albumin ≥ 2.5 mg/dL\n* INR ≤ 1.5 (not receiving anticoagulation therapy)\n* Creatinine normal or creatinine clearance ≥ 60 mL/min\n* Not pregnant or nursing\n* Negative pregnancy test\n* Fertile women must use effective contraception during and for four weeks after the last dose of AZD6244\n* Fertile men must use effective contraception during and for 16 weeks after the last dose of AZD6244\n* No significant traumatic injury within the past 3 weeks\n* No uncontrolled symptoms consistent with encephalopathy\n* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or its excipient, Captisol®\n* No QTc interval \\> 500 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., hypokalemia or family history of long QT interval syndrome), including NYHA class III-IV heart failure\n* No other malignancy within the past 3 years, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix\n* No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption\n* No uncontrolled concurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements\n* No malignant hypertension within the past year\n* No prior sorafenib or MEK inhibitors\n* More than 4 weeks since prior chemotherapy, biologic therapy, or immunotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered to ≤ grade 1 adverse events\n* No major surgery within the past 3 weeks\n* No other concurrent investigational agents\n* No concurrent requirement for medication that can prolong the QT interval\n* No concurrent combination antiretroviral therapy for HIV-positive patients\n* No concurrent consumption of grapefruit or grapefruit juice'}, 'identificationModule': {'nctId': 'NCT00553332', 'briefTitle': 'Selumetinib in Treating Patients With Biliary Cancer That Cannot Be Removed By Surgery', 'nctIdAliases': ['NCT01645644'], 'organization': {'class': 'NIH', 'fullName': 'National Cancer Institute (NCI)'}, 'officialTitle': 'A Phase 2 Study of AZD6244 in Biliary Cancers', 'orgStudyIdInfo': {'id': 'NCI-2009-00251'}, 'secondaryIdInfos': [{'id': 'OSU 07056'}, {'id': 'OSU-07056'}, {'id': 'CDR0000573452'}, {'id': 'N01CM62208', 'link': 'https://reporter.nih.gov/quickSearch/N01CM62208', 'type': 'NIH'}, {'id': 'N01CM62207', 'link': 'https://reporter.nih.gov/quickSearch/N01CM62207', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Treatment (enzyme inhibitor therapy)', 'description': 'Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.', 'interventionNames': ['Drug: selumetinib', 'Other: laboratory biomarker analysis']}], 'interventions': [{'name': 'selumetinib', 'type': 'DRUG', 'otherNames': ['ARRY-142886', 'AZD6244'], 'description': 'Given orally', 'armGroupLabels': ['Treatment (enzyme inhibitor therapy)']}, {'name': 'laboratory biomarker analysis', 'type': 'OTHER', 'description': 'Correlative studies', 'armGroupLabels': ['Treatment (enzyme inhibitor therapy)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '33612', 'city': 'Tampa', 'state': 'Florida', 'country': 'United States', 'facility': 'H. Lee Moffitt Cancer Center and Research Institute', 'geoPoint': {'lat': 27.94752, 'lon': -82.45843}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Emory University', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '48109-0352', 'city': 'Ann Arbor', 'state': 'Michigan', 'country': 'United States', 'facility': 'University of Michigan Cancer Center (UMCC) Research Base', 'geoPoint': {'lat': 42.27756, 'lon': -83.74088}}, {'zip': '48202', 'city': 'Detroit', 'state': 'Michigan', 'country': 'United States', 'facility': 'Wayne State University', 'geoPoint': {'lat': 42.33143, 'lon': -83.04575}}, {'zip': '27599', 'city': 'Chapel Hill', 'state': 'North Carolina', 'country': 'United States', 'facility': 'University of North Carolina', 'geoPoint': {'lat': 35.9132, 'lon': -79.05584}}, {'zip': '43210', 'city': 'Columbus', 'state': 'Ohio', 'country': 'United States', 'facility': 'Ohio State University Medical Center', 'geoPoint': {'lat': 39.96118, 'lon': -82.99879}}, {'zip': '37232', 'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'facility': 'Vanderbilt University', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}], 'overallOfficials': [{'name': 'Tanios Bekaii-Saab', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Ohio State University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}