Fingerprint Characterization Tyrosine Kinase Inhibitors in Advanced HCC

NCT03958669 | Terminated

• 1 other identifier: e:Med-HCC-2
• Study Type: observational
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma; Sorafenib

Keywords

Liver Cancer; Imaging; Molecular Charakterization; Tyrosine Kinase Inhibitor

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (11)

• Time needed to determine parameter based prediction of therapy outcome for single parameters and for multiscale modelling

  Diagnostic procedures at baseline and between week 3 and 6 after treatment initiation

• Progression Free Survival

  Median PFS is expected between 3.5 and 5.5 months

• Radiologically determined time to tumor progression (TTP)

  Median TTP is expected between 3.5 and 5.5 months

• Objective response rate (ORR) as measured by the sum of partial and complete responders.

  Within 6 months after treatment initiation

• Duration of tumor stabilization (CR, PR, SD)

  Through study completion, up to 18 months

Study Arms (1)

Sorafenib treated HCC patients

No intervention is performed. This is an observational study.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• HCC patients with indication for the treatment with an approved tyrosine kinase inhibitor, irrespective of previous systemic therapies.
• If prior systemic therapies had been applied, progression has to be documented prior to the start of treatment.
• Male or female ≥ 18 years and written informed consent.
• Histologically confirmed advanced stage hepatocellular carcinoma, BCLC class B or C.

You may not qualify if:

• ECOG performance status 0, 1 or 2.
• Life expectancy of 12 weeks or more.
• At least one measurable lesion without previous local therapy and that is suitable for accurate repeated measurements as per mRECIST guidelines.
• Adequate hematological parameters, as demonstrated by:
• Hemoglobin ≥ 9.0 g/dl (SI units: 5.6 mmol/l);
• WBC ≥ 2.5 x 109/l;
• Platelets ≥ 60 x 109/l;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 times upper limit of normal range (ULNR);
• Bilirubin ≤ 3 mg/dl;
• Serum creatinine ≤ 1.5 mg/dl (SI units: 132 µmol/l);
• Prothrombin Time (PT) International Normalized Ratio (INR) ≤ 1.5.
• Patients who meet any of the following criteria are not eligible for study participation:
• Renal failure requiring hemo- or peritoneal dialysis.
• Patients with no adequate treatment for gastrointestinal bleeding and esophagus varices within 14 days prior to study entry.
• Child-Pugh index class B in combination with more than slight ascites or hepatic encephalopathy \> Grade I.

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• German Federal Ministry of Education and Research: collaborator

Study Sites (1)

University Hospital Eberhard Karls University

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Biospecimen

Retention: SAMPLES WITH DNA

Tumor Biopsy, Circulating DNA, PBMCs, Circulating Metabolites

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Michael Bitzer, MD

  University Hospital, Eberhard Kars University Tübingen

  PRINCIPAL INVESTIGATOR

• Nisar P Malek, MD

  University Hospital, Eberhard Kars University Tübingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director Internal Medicine I

Study Record Dates

• First Submitted: December 16, 2018
• First Posted: May 22, 2019
• Study Start: November 1, 2019
• Primary Completion: December 31, 2022
• Study Completion: May 31, 2023
• Last Updated: April 1, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)