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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03958669
Other study ID # e:Med-HCC-2
Secondary ID
Status Terminated
Phase
First received
Last updated
Start date November 1, 2019
Est. completion date May 31, 2023

Study information

Verified date March 2024
Source University Hospital Tuebingen
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

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.


Description:

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 .


Recruitment information / eligibility

Status Terminated
Enrollment 2
Est. completion date May 31, 2023
Est. primary completion date December 31, 2022
Accepts healthy volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. HCC patients with indication for the treatment with an approved tyrosine kinase inhibitor, irrespective of previous systemic therapies. 2. If prior systemic therapies had been applied, progression has to be documented prior to the start of treatment. 3. Male or female = 18 years and written informed consent. 4. Histologically confirmed advanced stage hepatocellular carcinoma, BCLC class B or C. 5. 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). 6. ECOG performance status 0, 1 or 2. 7. Life expectancy of 12 weeks or more. 8. At least one measurable lesion without previous local therapy and that is suitable for accurate repeated measurements as per mRECIST guidelines. 9. Adequate hematological parameters, as demonstrated by: 10. Hemoglobin = 9.0 g/dl (SI units: 5.6 mmol/l); 11. WBC = 2.5 x 109/l; 12. Platelets = 60 x 109/l; 13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 5 times upper limit of normal range (ULNR); 14. Bilirubin = 3 mg/dl; 15. Serum creatinine = 1.5 mg/dl (SI units: 132 µmol/l); 16. Prothrombin Time (PT) International Normalized Ratio (INR) = 1.5. Exclusion Criteria: Patients who meet any of the following criteria are not eligible for study participation: 1. Renal failure requiring hemo- or peritoneal dialysis. 2. Patients with no adequate treatment for gastrointestinal bleeding and esophagus varices within 14 days prior to study entry. 3. Child-Pugh index class B in combination with more than slight ascites or hepatic encephalopathy > Grade I. 4. Altered mental status precluding understanding of the informed consent process.

Study Design


Locations

Country Name City State
Germany University Hospital Eberhard Karls University Tübingen BW

Sponsors (2)

Lead Sponsor Collaborator
University Hospital Tuebingen German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary To prospectively evaluate image fingerprint analysis of HCC tumor tissue to predict therapy responses MRI and CT scan, including radiomics analysis 6 months after therapy initiation
Primary To prospectively evaluate molecular fingerprint analysis of HCC tumor tissue to predict therapy responses Multiscale analysis of exome, transcriptome and metabolic Tumor characteristics 6 months after therapy initiation
Secondary Time needed to determine parameter based prediction of therapy outcome for single parameters and for multiscale modelling Days needed for prediction of therapy outcome by image, molecular and metabolic analysis Diagnostic procedures at baseline and between week 3 and 6 after treatment initiation
Secondary Progression Free Survival Months Median PFS is expected between 3.5 and 5.5 months
Secondary Radiologically determined time to tumor progression (TTP) Months Median TTP is expected between 3.5 and 5.5 months
Secondary Objective response rate (ORR) as measured by the sum of partial and complete responders. % of all treated patients Within 6 months after treatment initiation
Secondary Duration of tumor stabilization (CR, PR, SD) Days of duration of CR, PR or SD after diagnosis of best response Through study completion, up to 18 months
Secondary Overall Survival (OS) Months Current data suggest approximately 12 months
Secondary To prospectively assess patient-reported outcome of HCC patients under treatment with sorafenib EORTC QLQ-C30 questionnaire Through study completion, up to 18 months
Secondary Distribution of sorafenib adverse drug reactions CTCAE criteria Through study completion during sorafenib treatment, up to 18 months
Secondary Feasibility of detection of circulating miRNA Change of miRNA detection in peripheral blood sample between baseline and after treatment initiation Baseline and between week 3 and 6 after treatment initiation
Secondary Changes of Radiomics analysis under treatment with Sorafenib Collection of radiomics features of tumor tissue at baseline and after treatment initiation Baseline and between week 3 and 6 after treatment initiation
Secondary Changes of ultrasound elastography under treatment with Sorafenib Determination of ultrasound elastography of tumor tissue at baseline and after treatment initiation Baseline and between week 3 and 6 after treatment initiation
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