Ignite Creation Date:
2025-12-24 @ 10:54 PM
Ignite Modification Date:
2025-12-25 @ 8:23 PM
Study NCT ID:
NCT03958669
Status:
TERMINATED
Last Update Posted:
2024-04-01
First Post:
2018-12-16
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Fingerprint Characterization Tyrosine Kinase Inhibitors in Advanced HCC
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006528', 'term': 'Carcinoma, Hepatocellular'}, {'id': 'D008113', 'term': 'Liver Neoplasms'}], 'ancestors': [{'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008107', 'term': 'Liver Diseases'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Tumor Biopsy, Circulating DNA, PBMCs, Circulating Metabolites'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 2}, 'patientRegistry': False}, 'statusModule': {'whyStopped': 'Slow recruitment due to COVID-19 pandemic and several newly approved treatment options', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2019-11-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-03', 'completionDateStruct': {'date': '2023-05-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-03-28', 'studyFirstSubmitDate': '2018-12-16', 'studyFirstSubmitQcDate': '2019-05-17', 'lastUpdatePostDateStruct': {'date': '2024-04-01', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-05-22', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-12-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'To prospectively evaluate image fingerprint analysis of HCC tumor tissue to predict therapy responses', 'timeFrame': '6 months after therapy initiation', 'description': 'MRI and CT scan, including radiomics analysis'}, {'measure': 'To prospectively evaluate molecular fingerprint analysis of HCC tumor tissue to predict therapy responses', 'timeFrame': '6 months after therapy initiation', 'description': 'Multiscale analysis of exome, transcriptome and metabolic Tumor characteristics'}], 'secondaryOutcomes': [{'measure': 'Time needed to determine parameter based prediction of therapy outcome for single parameters and for multiscale modelling', 'timeFrame': 'Diagnostic procedures at baseline and between week 3 and 6 after treatment initiation', 'description': 'Days needed for prediction of therapy outcome by image, molecular and metabolic analysis'}, {'measure': 'Progression Free Survival', 'timeFrame': 'Median PFS is expected between 3.5 and 5.5 months', 'description': 'Months'}, {'measure': 'Radiologically determined time to tumor progression (TTP)', 'timeFrame': 'Median TTP is expected between 3.5 and 5.5 months', 'description': 'Months'}, {'measure': 'Objective response rate (ORR) as measured by the sum of partial and complete responders.', 'timeFrame': 'Within 6 months after treatment initiation', 'description': '% of all treated patients'}, {'measure': 'Duration of tumor stabilization (CR, PR, SD)', 'timeFrame': 'Through study completion, up to 18 months', 'description': 'Days of duration of CR, PR or SD after diagnosis of best response'}, {'measure': 'Overall Survival (OS)', 'timeFrame': 'Current data suggest approximately 12 months', 'description': 'Months'}, {'measure': 'To prospectively assess patient-reported outcome of HCC patients under treatment with sorafenib', 'timeFrame': 'Through study completion, up to 18 months', 'description': 'EORTC QLQ-C30 questionnaire'}, {'measure': 'Distribution of sorafenib adverse drug reactions', 'timeFrame': 'Through study completion during sorafenib treatment, up to 18 months', 'description': 'CTCAE criteria'}, {'measure': 'Feasibility of detection of circulating miRNA', 'timeFrame': 'Baseline and between week 3 and 6 after treatment initiation', 'description': 'Change of miRNA detection in peripheral blood sample between baseline and after treatment initiation'}, {'measure': 'Changes of Radiomics analysis under treatment with Sorafenib', 'timeFrame': 'Baseline and between week 3 and 6 after treatment initiation', 'description': 'Collection of radiomics features of tumor tissue at baseline and after treatment initiation'}, {'measure': 'Changes of ultrasound elastography under treatment with Sorafenib', 'timeFrame': 'Baseline and between week 3 and 6 after treatment initiation', 'description': 'Determination of ultrasound elastography of tumor tissue at baseline and after treatment initiation'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Liver Cancer', 'Imaging', 'Molecular Charakterization', 'Tyrosine Kinase Inhibitor'], 'conditions': ['Hepatocellular Carcinoma', 'Sorafenib']}, 'descriptionModule': {'briefSummary': 'This study is a prospective evaluation of a multiscale prediction model for the treatment with tyrosine kinase inhibitors (TKI) in HCC. Patients with HCC that qualify for systemic treatment with TKIs will be included. At baseline, prior to treatment, molecular and image fingerprints are collected (fingerprint #1). Further fingerprint investigations will be performed after a short treatment period at week 4 (fingerprint #2) and optional at tumor progression (Fingerprint #3). Based on previous findings from a preceding trial the fingerprint diagnostics #1 and #2 will be used to determine a prediction for treatment outcome at the earliest possible point in time ("therapy prediction"). This prediction will be compared to the prospectively determined outcome of the treated patients in this study (validation cohort; primary study endpoint). Fingerprint #3 will be optional to generate hypothesis for treatment failure.', 'detailedDescription': 'The aim of this prospective observational clinical study is to validate prognostic parameters for the treatment with tyrosine kinase inhibitors (TKI) that have been identified in a separate patient cohort with HCC (Study title "Fingerprint characterization of advanced HCC to optimize treatment decisions and enable an early prediction of therapy resistance", ClinicalTrials.gov Identifier NCT02372162). Based on these previous findings, predefined parameters that have been found to correlate with therapy responses will be determined for the patients in this observational trial. Diagnostic procedures include an image fingerprint (MRI and multi-phase CT scan of tumor manifestations, radiomics analysis of defined tumor areas, ultrasound elastography and a molecular fingerprint with exome and transcriptome sequencing from tumor tissue, single cell sequencing of PBMCs, MR spectroscopy for metabolomics analysis of blood and urine. These parameters at baseline will be used to predict therapy outcome, which will be prospectively compared to the clinical outcome under treatment with sorafenib. A second fingerprint will be collected at 4 weeks treatment and optional at tumor progression. New hypothesis generating parameters will be investigated in this patient cohort .'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'We will prospectively enrol all patients with HCC at our institution that qualify for a systemic treatment with sorafenib that fulfil the inclusion and exclusion criteria.', 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. HCC patients with indication for the treatment with an approved tyrosine kinase inhibitor, irrespective of previous systemic therapies.\n2. If prior systemic therapies had been applied, progression has to be documented prior to the start of treatment.\n3. Male or female ≥ 18 years and written informed consent.\n4. Histologically confirmed advanced stage hepatocellular carcinoma, BCLC class B or C.\n5. Child-Pugh class A or B. Only patients with Child-Pugh index class B of not more than 7 will be included. Patients with untreatable ascites or hepatic encephalopathy \\> Grade 1 are excluded (see exclusion criteria).\n6. ECOG performance status 0, 1 or 2.\n7. Life expectancy of 12 weeks or more.\n8. At least one measurable lesion without previous local therapy and that is suitable for accurate repeated measurements as per mRECIST guidelines.\n9. Adequate hematological parameters, as demonstrated by:\n10. Hemoglobin ≥ 9.0 g/dl (SI units: 5.6 mmol/l);\n11. WBC ≥ 2.5 x 109/l;\n12. Platelets ≥ 60 x 109/l;\n13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 times upper limit of normal range (ULNR);\n14. Bilirubin ≤ 3 mg/dl;\n15. Serum creatinine ≤ 1.5 mg/dl (SI units: 132 µmol/l);\n16. Prothrombin Time (PT) International Normalized Ratio (INR) ≤ 1.5.\n\nExclusion Criteria:\n\nPatients who meet any of the following criteria are not eligible for study participation:\n\n1. Renal failure requiring hemo- or peritoneal dialysis.\n2. Patients with no adequate treatment for gastrointestinal bleeding and esophagus varices within 14 days prior to study entry.\n3. Child-Pugh index class B in combination with more than slight ascites or hepatic encephalopathy \\> Grade I.\n4. Altered mental status precluding understanding of the informed consent process.'}, 'identificationModule': {'nctId': 'NCT03958669', 'acronym': 'e:Med-HCC-2', 'briefTitle': 'Fingerprint Characterization Tyrosine Kinase Inhibitors in Advanced HCC', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital Tuebingen'}, 'officialTitle': 'Prospective Evaluation of Image and Molecular Fingerprint Characterization to Guide Treatment With Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma', 'orgStudyIdInfo': {'id': 'e:Med-HCC-2'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Sorafenib treated HCC patients', 'description': 'No intervention is performed. This is an observational study.'}]}, 'contactsLocationsModule': {'locations': [{'zip': '72076', 'city': 'Tübingen', 'state': 'Baden-Wurttemberg', 'country': 'Germany', 'facility': 'University Hospital Eberhard Karls University', 'geoPoint': {'lat': 48.52266, 'lon': 9.05222}}], 'overallOfficials': [{'name': 'Michael Bitzer, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospital, Eberhard Kars University Tübingen'}, {'name': 'Nisar P Malek, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospital, Eberhard Kars University Tübingen'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital Tuebingen', 'class': 'OTHER'}, 'collaborators': [{'name': 'German Federal Ministry of Education and Research', 'class': 'OTHER_GOV'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Director Internal Medicine I', 'investigatorFullName': 'Prof. Dr. Michael Bitzer', 'investigatorAffiliation': 'University Hospital Tuebingen'}}}}