Ignite Creation Date:
2025-12-25 @ 2:50 AM
Ignite Modification Date:
2026-03-06 @ 2:40 AM
Study NCT ID:
NCT00875433
Status:
COMPLETED
Last Update Posted:
2013-12-30
First Post:
2009-04-02
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Afatinib (BIBW 2992) QTcF Trial in Patients With Relapsed or Refractory Solid Tumours
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009369', 'term': 'Neoplasms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077716', 'term': 'Afatinib'}], 'ancestors': [{'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011799', 'term': 'Quinazolines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clintriage.rdg@boehringer-ingelheim.com', 'phone': '1-800-243-0127', 'title': 'Boehringer Ingelheim Call Center', 'organization': 'Boehringer Ingelheim Pharmaceuticals'}, 'certainAgreement': {'otherDetails': 'Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'First administration of trial medication until 28 days after last administration of trial medication', 'eventGroups': [{'id': 'EG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)', 'otherNumAtRisk': 60, 'otherNumAffected': 58, 'seriousNumAtRisk': 60, 'seriousNumAffected': 34}], 'otherEvents': [{'term': 'Ocular effect', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 8}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 6}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Abdominal pain upper', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 10}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 44}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Dyspepsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Dysphagia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Nausea/Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 28}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Stomatitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 27}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Oedema peripheral', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 5}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 7}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Lower respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Nail effect', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 8}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 5}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Decreased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 23}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Dehydration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 6}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Muscle spasms', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 31}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Dysuria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 5}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 8}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Dyspnoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 6}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Epistaxis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 9}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Haemoptysis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Oropharyngeal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Dry skin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 8}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Palmar-plantar erythrodysaesthesia syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 7}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Rash/acne', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 45}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}], 'seriousEvents': [{'term': 'Anaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 2}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Cardiac arrest', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Myocardial ischaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Tachycardia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Abdominal pain lower', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Abdominal pain upper', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 7}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Duodenal ulcer', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Dysphagia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Nausea/Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 6}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Small intestinal obstruction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Stomatitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Cellulitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Lower respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Lung infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Urosepsis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Electrocardiogram QT prolonged', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Decreased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Dehydration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 5}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Hyponatraemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Hypovolaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Metastases to central nervous system', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Neoplasm malignant', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 4}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Peritoneal neoplasm', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Rectal cancer metastatic', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Convulsion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Confusional state', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Renal disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Renal insufficency', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 5}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Urinary retention', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Dyspnoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Dyspnoea exertional', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Pleural effusion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Pulmonary embolism', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Palmar-plantar erythrodysaesthesia syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Rash/acne', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 2}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}, {'term': 'Ureteric obstruction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 60, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 14.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Objective Response (OR)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '60', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.', 'description': 'OR is defined as complete response and partial response (PR) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST) for solid tumours (excluding glioblastomas).', 'unitOfMeasure': 'Participants with OR', 'reportingStatus': 'POSTED', 'populationDescription': 'Treated Set (TS). TS consisted of all patients who received at least one dose of trial medication.'}, {'type': 'PRIMARY', 'title': 'Average Time-matched QT Corrected by the Fridericia Formula (QTcF) Change From Baseline to Day 14', 'denoms': [{'units': 'Participants', 'counts': [{'value': '49', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.3', 'spread': '1.5', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'The day before the first drug dose (baseline) and the day 14. Electrocardiograms (ECG) were performed at time point 0 and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h, 24 h thereafter.', 'description': 'Average time-matched QT corrected by the Fridericia formula (QTcF) change from baseline to day 14 over 1 to 24 hours following administration of afatinib.', 'unitOfMeasure': 'ms', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients in TS who had at least 1 time-matched pair of QT measurements available from baseline and from Day 14 of treatment.'}, {'type': 'SECONDARY', 'title': 'Progression-free Survival (PFS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '53', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '10.6', 'groupId': 'OG000', 'lowerLimit': '7.4', 'upperLimit': '15.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.', 'description': 'PFS was defined as the time from the first treatment to the occurrence of tumour progression or death, whichever came first. It was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas) as well as by the investigators assessment. Median time results from unstratified Kaplan-Meier estimates.', 'unitOfMeasure': 'weeks', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients from TS who progressed or died.'}, {'type': 'SECONDARY', 'title': 'Overall Survival (OS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '53', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '39.6', 'groupId': 'OG000', 'lowerLimit': '23.3', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.', 'description': 'Overall survival (OS) is defined as time from start of treatment to death.', 'unitOfMeasure': 'weeks', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'TS.'}, {'type': 'SECONDARY', 'title': 'Disease Control', 'denoms': [{'units': 'Participants', 'counts': [{'value': '60', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '32', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.', 'description': 'Disease control was defined as CR, PR or stable disease (SD) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas).', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'TS.'}, {'type': 'SECONDARY', 'title': 'Duration of Disease Control (DC)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '15.3', 'groupId': 'OG000', 'lowerLimit': '15.0', 'upperLimit': '24.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.', 'description': 'Duration of Disease control (DC). DC was defined as CR, PR or stable disease (SD) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas).', 'unitOfMeasure': 'weeks', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'TS.'}, {'type': 'SECONDARY', 'title': 'Patients With Notable Findings in QTcF on Day 14', 'denoms': [{'units': 'Participants', 'counts': [{'value': '51', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Day 14', 'description': 'Notable findings are defined as a QTcF\\>500 ms or an increase in QTcF of \\>60ms.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients from TS with data for QTcF on day 14'}, {'type': 'SECONDARY', 'title': 'Patients With Clinically Relevant Findings in ECG on Day 14', 'denoms': [{'units': 'Participants', 'counts': [{'value': '51', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Day 14', 'description': 'Patients with clinically relevant findings in Electrocardiogram data (ECG) on day 14.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients from TS with data for ECG on day 14'}, {'type': 'SECONDARY', 'title': 'Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point', 'denoms': [{'units': 'Participants', 'counts': [{'value': '49', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'title': 'Time-point 1:00 h (N=48)', 'categories': [{'measurements': [{'value': '1.6', 'spread': '2.2', 'groupId': 'OG000'}]}]}, {'title': 'Time-point 2:00 h (N=48)', 'categories': [{'measurements': [{'value': '1.2', 'spread': '2.2', 'groupId': 'OG000'}]}]}, {'title': 'Time-point 3:00 h (N=49)', 'categories': [{'measurements': [{'value': '-2.1', 'spread': '2.2', 'groupId': 'OG000'}]}]}, {'title': 'Time-point 4:00 h (N=49)', 'categories': [{'measurements': [{'value': '-2.5', 'spread': '2.2', 'groupId': 'OG000'}]}]}, {'title': 'Time-point 5:00 h (N=49)', 'categories': [{'measurements': [{'value': '-2.3', 'spread': '2.2', 'groupId': 'OG000'}]}]}, {'title': 'Time-point 6:00 h (N=49)', 'categories': [{'measurements': [{'value': '-0.4', 'spread': '2.2', 'groupId': 'OG000'}]}]}, {'title': 'Time-point 7:00 h (N=48)', 'categories': [{'measurements': [{'value': '0.2', 'spread': '2.2', 'groupId': 'OG000'}]}]}, {'title': 'Time-point 10:00 h (N=49)', 'categories': [{'measurements': [{'value': '0.2', 'spread': '2.2', 'groupId': 'OG000'}]}]}, {'title': 'Time-point 24:00 h (N=48)', 'categories': [{'measurements': [{'value': '0.6', 'spread': '2.2', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and day 14 (at 1, 2, 3, 4, 5, 6, 7, 10, 24 hours post-dose )', 'description': 'Individual QTcF measurements at each time-point. Response was defined as the change from baseline. Analysis adjusted for baseline using a mixed model.', 'unitOfMeasure': 'ms', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients in TS who had at least 1 time-matched pair of QT measurements available from either Day1 or Day 14 of treatment.'}, {'type': 'SECONDARY', 'title': 'Average Time-matched QT Change From Baseline to Day 14', 'denoms': [{'units': 'Participants', 'counts': [{'value': '49', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.4', 'spread': '2.6', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'The day before the first drug dose (baseline) and the day 14. Electrocardiograms (ECG) were performed at time point 0 and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h, 24 h thereafter.', 'description': 'Average time-matched QT change from baseline to day 14 over 1 to 24 hours following administration of afatinib.', 'unitOfMeasure': 'ms', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients in TS who had at least 1 time-matched pair of QT measurements available from baseline and from Day 14 of treatment.'}, {'type': 'SECONDARY', 'title': 'Patients With Notable Findings in QT on Day 14', 'denoms': [{'units': 'Participants', 'counts': [{'value': '51', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Day 14', 'description': 'Number of Patients with notable findings in QT on day 14. Notable findings are defined as a QT\\>500 ms.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients from TS with data for QTcF on day 14'}, {'type': 'SECONDARY', 'title': 'Average Time-matched Heart Rate Change From Baseline to Day 14.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '49', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '0.1', 'spread': '1.2', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'The day before the first drug dose (baseline) and the day 14.', 'description': 'Average time-matched heart rate change from baseline to day 14.', 'unitOfMeasure': 'bpm', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients in TS who had at least 1 time-matched pair of QT measurements available from baseline and from Day 14 of treatment.'}, {'type': 'SECONDARY', 'title': 'Highest CTC Grade for Adverse Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '60', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'title': 'Grade 1', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Grade 2', 'categories': [{'measurements': [{'value': '19', 'groupId': 'OG000'}]}]}, {'title': 'Grade 3', 'categories': [{'measurements': [{'value': '27', 'groupId': 'OG000'}]}]}, {'title': 'Grade 4', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}]}]}, {'title': 'Grade 5', 'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'First administration of trial medication until 28 days after last administration of trial medication', 'description': 'Highest Common Terminology Criteria (CTC) grade for adverse events', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients from TS with adverse events'}, {'type': 'SECONDARY', 'title': 'Area Under Curve 0-24 Hours (AUC0-24) on Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '56', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '482', 'spread': '55.6', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1', 'description': 'AUC0-24 represents the area under the concentration curve of afatinib in plasma from 0 to 24 hours on Day 1.', 'unitOfMeasure': 'ng*h/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'TS.'}, {'type': 'SECONDARY', 'title': 'Maximum Concentration (Cmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '60', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '44.7', 'spread': '58.9', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1', 'description': 'Cmax represents the maximum measured concentration of afatinib in plasma on Day 1.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'TS.'}, {'type': 'SECONDARY', 'title': 'Time From Dosing to the Maximum Concentration (Tmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '60', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '3.06', 'groupId': 'OG000', 'lowerLimit': '0.900', 'upperLimit': '6.17'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1', 'description': 'tmax represents the time from dosing to the maximum concentration of afatinib in plasma on Day 1.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'TS.'}, {'type': 'SECONDARY', 'title': 'Area Under Curve of Afatinib Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '1250', 'spread': '53.3', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14', 'description': 'AUCtau,ss represents the area under the concentration curve of afatinib in plasma over a uniform dosing interval tau (24h) at steady state (Day14).', 'unitOfMeasure': 'ng*h/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'TS.'}, {'type': 'SECONDARY', 'title': 'Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '86.6', 'spread': '55.2', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14', 'description': 'Cmax,ss represents the maximum measured concentration of afatinib in plasma at steady state (Day 14).', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'TS.'}, {'type': 'SECONDARY', 'title': 'Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '3.07', 'groupId': 'OG000', 'lowerLimit': '1.00', 'upperLimit': '7.05'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14', 'description': 'tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state (Day 14).', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Subset of TS, restricted to patients with adequate protocol compliance, i.e. patients without important protocol violations.'}, {'type': 'SECONDARY', 'title': 'Accumulation Ratio of AUC Values (R_A,AUC)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '2.67', 'spread': '53.4', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1 and 14', 'description': 'R\\_A,AUC represents the accumulation ratio of AUC values after multiple dose administration over a uniform dosing interval t between days 1 and 14', 'unitOfMeasure': 'ratio', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Subset of TS, restricted to patients with adequate protocol compliance, i.e. patients without important protocol violations.'}, {'type': 'SECONDARY', 'title': 'Accumulation Ratio of AUC Values (R_A,Cmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '2.05', 'spread': '58.5', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1 and 14', 'description': 'R\\_A,Cmax represents the accumulation ratio of Cmax values after multiple dose administration over a uniform dosing interval t between days 1 and 14', 'unitOfMeasure': 'ratio', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Subset of TS, restricted to patients with adequate protocol compliance, i.e. patients without important protocol violations.'}, {'type': 'SECONDARY', 'title': 'Percentage Peak Trough Fluctuation (PTF)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'classes': [{'categories': [{'measurements': [{'value': '97.6', 'spread': '37.8', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14', 'description': 'PTF represents the percentage peak trough fluctuation. PTF is defined as difference between maximum and minimum concentration at steady state divided by the average concentration multiplied with 100 to report as percentage.', 'unitOfMeasure': 'percentage of peak trough fluctuation', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Subset of TS, restricted to patients with adequate protocol compliance, i.e. patients without important protocol violations.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'Treated', 'groupId': 'FG000', 'numSubjects': '60'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '60'}]}], 'dropWithdraws': [{'type': 'Progressive disease', 'reasons': [{'groupId': 'FG000', 'numSubjects': '41'}]}, {'type': 'Other Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '14'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'Other', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '60', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'All Patients', 'description': 'Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '58.7', 'spread': '11.9', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '30', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '30', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 60}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-03'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-10', 'lastUpdateSubmitDate': '2013-12-05', 'studyFirstSubmitDate': '2009-04-02', 'resultsFirstSubmitDate': '2013-08-08', 'studyFirstSubmitQcDate': '2009-04-02', 'lastUpdatePostDateStruct': {'date': '2013-12-30', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2013-10-21', 'studyFirstPostDateStruct': {'date': '2009-04-03', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2013-11-13', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Objective Response (OR)', 'timeFrame': 'Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.', 'description': 'OR is defined as complete response and partial response (PR) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST) for solid tumours (excluding glioblastomas).'}, {'measure': 'Average Time-matched QT Corrected by the Fridericia Formula (QTcF) Change From Baseline to Day 14', 'timeFrame': 'The day before the first drug dose (baseline) and the day 14. Electrocardiograms (ECG) were performed at time point 0 and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h, 24 h thereafter.', 'description': 'Average time-matched QT corrected by the Fridericia formula (QTcF) change from baseline to day 14 over 1 to 24 hours following administration of afatinib.'}], 'secondaryOutcomes': [{'measure': 'Progression-free Survival (PFS)', 'timeFrame': 'Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.', 'description': 'PFS was defined as the time from the first treatment to the occurrence of tumour progression or death, whichever came first. It was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas) as well as by the investigators assessment. Median time results from unstratified Kaplan-Meier estimates.'}, {'measure': 'Overall Survival (OS)', 'timeFrame': 'Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.', 'description': 'Overall survival (OS) is defined as time from start of treatment to death.'}, {'measure': 'Disease Control', 'timeFrame': 'Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.', 'description': 'Disease control was defined as CR, PR or stable disease (SD) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas).'}, {'measure': 'Duration of Disease Control (DC)', 'timeFrame': 'Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.', 'description': 'Duration of Disease control (DC). DC was defined as CR, PR or stable disease (SD) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas).'}, {'measure': 'Patients With Notable Findings in QTcF on Day 14', 'timeFrame': 'Day 14', 'description': 'Notable findings are defined as a QTcF\\>500 ms or an increase in QTcF of \\>60ms.'}, {'measure': 'Patients With Clinically Relevant Findings in ECG on Day 14', 'timeFrame': 'Day 14', 'description': 'Patients with clinically relevant findings in Electrocardiogram data (ECG) on day 14.'}, {'measure': 'Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point', 'timeFrame': 'Baseline and day 14 (at 1, 2, 3, 4, 5, 6, 7, 10, 24 hours post-dose )', 'description': 'Individual QTcF measurements at each time-point. Response was defined as the change from baseline. Analysis adjusted for baseline using a mixed model.'}, {'measure': 'Average Time-matched QT Change From Baseline to Day 14', 'timeFrame': 'The day before the first drug dose (baseline) and the day 14. Electrocardiograms (ECG) were performed at time point 0 and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h, 24 h thereafter.', 'description': 'Average time-matched QT change from baseline to day 14 over 1 to 24 hours following administration of afatinib.'}, {'measure': 'Patients With Notable Findings in QT on Day 14', 'timeFrame': 'Day 14', 'description': 'Number of Patients with notable findings in QT on day 14. Notable findings are defined as a QT\\>500 ms.'}, {'measure': 'Average Time-matched Heart Rate Change From Baseline to Day 14.', 'timeFrame': 'The day before the first drug dose (baseline) and the day 14.', 'description': 'Average time-matched heart rate change from baseline to day 14.'}, {'measure': 'Highest CTC Grade for Adverse Events', 'timeFrame': 'First administration of trial medication until 28 days after last administration of trial medication', 'description': 'Highest Common Terminology Criteria (CTC) grade for adverse events'}, {'measure': 'Area Under Curve 0-24 Hours (AUC0-24) on Day 1', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1', 'description': 'AUC0-24 represents the area under the concentration curve of afatinib in plasma from 0 to 24 hours on Day 1.'}, {'measure': 'Maximum Concentration (Cmax)', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1', 'description': 'Cmax represents the maximum measured concentration of afatinib in plasma on Day 1.'}, {'measure': 'Time From Dosing to the Maximum Concentration (Tmax)', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1', 'description': 'tmax represents the time from dosing to the maximum concentration of afatinib in plasma on Day 1.'}, {'measure': 'Area Under Curve of Afatinib Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss)', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14', 'description': 'AUCtau,ss represents the area under the concentration curve of afatinib in plasma over a uniform dosing interval tau (24h) at steady state (Day14).'}, {'measure': 'Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14', 'description': 'Cmax,ss represents the maximum measured concentration of afatinib in plasma at steady state (Day 14).'}, {'measure': 'Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss)', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14', 'description': 'tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state (Day 14).'}, {'measure': 'Accumulation Ratio of AUC Values (R_A,AUC)', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1 and 14', 'description': 'R\\_A,AUC represents the accumulation ratio of AUC values after multiple dose administration over a uniform dosing interval t between days 1 and 14'}, {'measure': 'Accumulation Ratio of AUC Values (R_A,Cmax)', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1 and 14', 'description': 'R\\_A,Cmax represents the accumulation ratio of Cmax values after multiple dose administration over a uniform dosing interval t between days 1 and 14'}, {'measure': 'Percentage Peak Trough Fluctuation (PTF)', 'timeFrame': '0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14', 'description': 'PTF represents the percentage peak trough fluctuation. PTF is defined as difference between maximum and minimum concentration at steady state divided by the average concentration multiplied with 100 to report as percentage.'}]}, 'conditionsModule': {'conditions': ['Neoplasms']}, 'descriptionModule': {'briefSummary': 'A phase II trial to assess the impact of afatinib (BIBW 2992) on the heart (QTcF) and the effectiveness of afatinib (BIBW 2992) in treating certain cancers. Cancers studied will include glioblastoma and cancers which have spread to the brain (metastases).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion criteria:\n\n1. Male or female patients aged at least 18 years old.\n2. Histologically or cytologically confirmed diagnosis of a solid malignant tumour, known to express EGFR/HER2 that is either refractory to standard therapies, or for which no standard treatment is available (including patients with brain metastases).\n3. At least one tumor lesion that can accurately be measured by computed tomography (CT) or magnetic resonance imaging (MRI) in at least one dimension with longest diameter to be recorded as greater than or equal to 20 mm using conventional techniques or greater than or equal to 10 mm with spiral CT scan.\n4. Life expectancy of at least 3 months.\n5. Written informed consent that is consistent with ICH-GCP guidelines.\n6. Eastern Cooperative Oncology Group (ECOG) performance score 0,1 or 2.\n7. Patients must have recovered from any previous surgery.\n8. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) for the duration of trial participation. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days of trial enrolment. Breast feeding mothers will be excluded since these agents may be toxic to infants.\n\nFor patients with Glioma and brain metastases the following additional inclusion criteria should apply:\n\n1. Histologically-confirmed WHO Grade IV malignant glioma at first episode of recurrence after prior combined chemo-radiotherapy. Patients with prior low-grade glioma are eligible if histological assessment demonstrates transformation to WHO Grade IV malignant glioma.\n2. Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on Gd MRI performed within 14 days prior to first treatment (Day 1).\n\nExclusion criteria:\n\nMajor exclusion criteria; 9. Radiotherapy within the past 2 weeks prior to treatment with the trial drug. 10. Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance non-cancer therapy) or immunotherapy within the past 4 weeks before first drug administration.\n\n11\\. Patients not completely recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies to CTC \\< Grade 1. Prior chemotherapy is allowed if completed at least 4 weeks prior to first trial treatment (6 weeks for mitomycin C or nitrosoureas) and the patient has recovered from the acute toxicities of that therapy.\n\n12\\. Prior treatment with EGFR targeting therapies or treatment with EGFR- or HER2 inhibiting drugs within the past four weeks before start of therapy or concomitantly with this trial.\n\n15\\. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, including New York Heart Association (NYHA) functional classification of 3.\n\n16\\. Cardiac left ventricular function with resting ejection fraction \\< 50% measured by multigated blood pool imaging of the heart (MUGA scan) or Echocardiogram.\n\n17\\. QTcF- interval \\> 470 ms at screening. 18. PR-interval \\> 230 ms at screening. 19. QRS-interval \\>120 ms at screening. 20. ST-segment and T/U-wave abnormalities at screening, as will be assessed by a cardiology specialist of a central lab.\n\n21\\. Absolute neutrophil count (ANC) \\< 1,500/mm3. 22. Platelet count \\< 100,000 / mm3. 23. Bilirubin \\> 1.5 mg / dl (\\>26 micro mol / L, SI unit equivalent). Aspartate amino transferase (AST) or alanine amino transferase (ALT) \\> or equal to three times the upper limit of normal (if related to liver metastases \\> five times the upper limit of normal).\n\n24\\. Serum creatinine \\> 1.5 times of the upper normal limit or calculated/measured creatinine clearance \\> or equal to 45 ml / min.\n\n25\\. Patients with known Interstitial Lung Disease (ILD) For Patients with glioma and brain metastases additional exclusion criteria apply;\n\n1. Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least four (4) weeks, no history of cerebral oedema or bleeding in the past four (4) weeks. Steroids will be allowed. Anti-epileptic therapy will be allowed if no changes are anticipated within the initial 14 days of treatment (QTC-evaluation).\n2. Less than 4 weeks between radiotherapy and start of study treatment, unless new enhancing lesion outside of radiation field or radiologically progressive on two consecutive MRI scans at least four weeks apart or biopsy-proven recurrence.\n3. Less than two weeks from surgical resection (one week from prior stereotactic biopsy) or major surgical procedure.\n4. Less than two weeks after previous chemotherapy (6 weeks from nitrosureas).\n5. Less than four weeks from prior treatment with bevacizumab.\n6. Treatment with other investigational drugs; participation in another clinical study within the past 2 weeks before start of therapy or concomitantly with this study.'}, 'identificationModule': {'nctId': 'NCT00875433', 'briefTitle': 'Afatinib (BIBW 2992) QTcF Trial in Patients With Relapsed or Refractory Solid Tumours', 'organization': {'class': 'INDUSTRY', 'fullName': 'Boehringer Ingelheim'}, 'officialTitle': 'Phase II Open Label Trial to Assess the Efficacy and the Impact on QTcF of Continuous Oral BIBW 2992 at a Daily Dose of 50mg in Patients With Relapsed or Refractory Solid Tumours Including Patients With Brain Metastases and Those With Glioblastoma Not Amenable to Other Therapy', 'orgStudyIdInfo': {'id': '1200.24'}, 'secondaryIdInfos': [{'id': '2008-006288-36', 'type': 'EUDRACT_NUMBER', 'domain': 'EudraCT'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Monotherapy', 'description': 'BIBW 2992 high dose, once daily, continuous, monotherapy', 'interventionNames': ['Drug: BIBW 2992']}], 'interventions': [{'name': 'BIBW 2992', 'type': 'DRUG', 'description': 'patients to receive continuous oral daily dosing of BIBW 2992', 'armGroupLabels': ['Monotherapy']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Guildford', 'country': 'United Kingdom', 'facility': '1200.24.4403 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 51.23536, 'lon': -0.57427}}, {'city': 'London', 'country': 'United Kingdom', 'facility': '1200.24.4402 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'city': 'London', 'country': 'United Kingdom', 'facility': '1200.24.4404 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'city': 'Sutton', 'country': 'United Kingdom', 'facility': '1200.24.4401 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 51.35, 'lon': -0.2}}], 'overallOfficials': [{'name': 'Boehringer Ingelheim', 'role': 'STUDY_CHAIR', 'affiliation': 'Boehringer Ingelheim'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Boehringer Ingelheim', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}