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Fingerprint Characterization of Sorafenib Treated HCC (HCC-e:Med2)

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ClinicalTrials.gov Identifier: NCT03958669
Recruitment Status : Not yet recruiting
First Posted : May 22, 2019
Last Update Posted : June 19, 2019
Sponsor:
Collaborator:
German Federal Ministry of Education and Research
Information provided by (Responsible Party):
Prof. Dr. Michael Bitzer, University Hospital Tuebingen

Brief Summary:
This study is a prospective evaluation of a multiscale prediction model for the treatment with sorafenib in HCC. Patients with HCC that qualify for systemic treatment with sorafenib will be included. At baseline, prior to sorafenib 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.

Condition or disease
Hepatocellular Carcinoma Sorafenib

Detailed Description:
The aim of this prospective observational clinical study is to validate prognostic parameters for the treatment with sorafenib 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, liquid biopsy for circulating tumor DNA and miRNA, 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 (circulating miRNA, liquid biopsy of predefined genetic alterations, ultrasound elastography of liver tumor areas).

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Evaluation of Image and Molecular Fingerprint Characterization to Guide Treatment With Sorafenib in Hepatocellular Carcinoma
Estimated Study Start Date : July 1, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine


Group/Cohort
Sorafenib treated HCC patients
No intervention is performed. This is an observational study.



Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. Progression Free Survival [ Time Frame: Median PFS is expected between 3.5 and 5.5 months ]
    Months

  3. Radiologically determined time to tumor progression (TTP) [ Time Frame: Median TTP is expected between 3.5 and 5.5 months ]
    Months

  4. 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

  5. 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

  6. Overall Survival (OS) [ Time Frame: Current data suggest approximately 12 months ]
    Months

  7. 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

  8. Distribution of sorafenib adverse drug reactions [ Time Frame: Through study completion during sorafenib treatment, up to 18 months ]
    CTCAE criteria

  9. 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

  10. 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

  11. 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


Biospecimen Retention:   Samples With DNA
Tumor Biopsy, Circulating DNA, Circulating Metabolites, Circulating miRNA


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.
Criteria

Inclusion Criteria:

  1. HCC patients with indication for the treatment with sorafenib, irrespective of previous systemic therapies.
  2. If prior systemic therapies had been applied, progression has to be documented prior to the start of treatment with sorafenib.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03958669


Contacts
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Contact: Ursula Koppenhöfer, Dipl. biol. +497071 ext 2984457 ursula.koppenhoefer@med.uni-tuebingen.de

Sponsors and Collaborators
University Hospital Tuebingen
German Federal Ministry of Education and Research
Investigators
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Principal Investigator: Michael Bitzer, MD University Hospital, Eberhard Kars University Tübingen
Principal Investigator: Nisar P Malek, MD University Hospital, Eberhard Kars University Tübingen

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Responsible Party: Prof. Dr. Michael Bitzer, Associate Director Internal Medicine I, University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT03958669     History of Changes
Other Study ID Numbers: e:Med-HCC-2
First Posted: May 22, 2019    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Prof. Dr. Michael Bitzer, University Hospital Tuebingen:
Sorafenib
Liver Cancer
Imaging
Molecular Charakterization
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action