Fingerprint Characterization Tyrosine Kinase Inhibitors in Advanced HCC

NCT ID: NCT03958669

Last Updated: 2024-04-01

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 2 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-11-01
• Study Completion Date: 2023-05-31

Brief 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.

Detailed 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 .

Conditions

Hepatocellular Carcinoma; Sorafenib

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Sorafenib treated HCC patients

No intervention is performed. This is an observational study.

No interventions assigned to this group

Eligibility Criteria

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.

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Michael Bitzer

Associate Director Internal Medicine I

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Bitzer, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Eberhard Kars University Tübingen

Nisar P Malek, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Eberhard Kars University Tübingen

Locations

University Hospital Eberhard Karls University

Tübingen, Baden-Wurttemberg, Germany

Countries

Germany

Other Identifiers

e:Med-HCC-2

Identifier Type: -

Identifier Source: org_study_id