Fingerprint Characterization Tyrosine Kinase Inhibitors in Advanced HCC (e:Med-HCC-2)

March 28, 2024 updated by: Prof. Dr. Michael Bitzer, University Hospital Tuebingen

Prospective Evaluation of Image and Molecular Fingerprint Characterization to Guide Treatment With Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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 .

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Germany
    • BW
      • Tübingen, BW, Germany, 72076
        • University Hospital Eberhard Karls University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

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.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Sorafenib treated HCC patients
No intervention is performed. This is an observational study.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To prospectively evaluate image fingerprint analysis of HCC tumor tissue to predict therapy responses
Time Frame: 6 months after therapy initiation
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
Time Frame: 6 months after therapy initiation
Multiscale analysis of exome, transcriptome and metabolic Tumor characteristics
6 months after therapy initiation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time needed to determine parameter based prediction of therapy outcome for single parameters and for multiscale modelling
Time Frame: Diagnostic procedures at baseline and between week 3 and 6 after treatment initiation
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
Progression Free Survival
Time Frame: Median PFS is expected between 3.5 and 5.5 months
Months
Median PFS is expected between 3.5 and 5.5 months
Radiologically determined time to tumor progression (TTP)
Time Frame: Median TTP is expected between 3.5 and 5.5 months
Months
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.
Time Frame: Within 6 months after treatment initiation
% of all treated patients
Within 6 months after treatment initiation
Duration of tumor stabilization (CR, PR, SD)
Time Frame: Through study completion, up to 18 months
Days of duration of CR, PR or SD after diagnosis of best response
Through study completion, up to 18 months
Overall Survival (OS)
Time Frame: Current data suggest approximately 12 months
Months
Current data suggest approximately 12 months
To prospectively assess patient-reported outcome of HCC patients under treatment with sorafenib
Time Frame: Through study completion, up to 18 months
EORTC QLQ-C30 questionnaire
Through study completion, up to 18 months
Distribution of sorafenib adverse drug reactions
Time Frame: Through study completion during sorafenib treatment, up to 18 months
CTCAE criteria
Through study completion during sorafenib treatment, up to 18 months
Feasibility of detection of circulating miRNA
Time Frame: Baseline and between week 3 and 6 after treatment initiation
Change of miRNA detection in peripheral blood sample between baseline and after treatment initiation
Baseline and between week 3 and 6 after treatment initiation
Changes of Radiomics analysis under treatment with Sorafenib
Time Frame: Baseline and between week 3 and 6 after treatment initiation
Collection of radiomics features of tumor tissue at baseline and after treatment initiation
Baseline and between week 3 and 6 after treatment initiation
Changes of ultrasound elastography under treatment with Sorafenib
Time Frame: Baseline and between week 3 and 6 after treatment initiation
Determination of ultrasound elastography of tumor tissue at baseline and after treatment initiation
Baseline and between week 3 and 6 after treatment initiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Tuebingen

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
German Federal Ministry of Education and Research

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael Bitzer, MD, University Hospital, Eberhard Kars University Tübingen
  • Principal Investigator: Nisar P Malek, MD, University Hospital, Eberhard Kars University Tübingen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 16, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 17, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 22, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 1, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 28, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • e:Med-HCC-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings