Characterization of Baseline Biomarker Variability in Participants With Hepatocellular Carcinoma (MK-0000-215)

Overview

The purpose of this study is to characterize the baseline variability of a panel of tissue (tumor and adjacent) and blood-based biomarkers obtained from participants with hepatocellular carcinoma (HCC). The primary hypothesis is that the upper bound of the 80% Confidence Interval of log beta-catenin protein or messenger RNA (mRNA) expression from one core needle biopsy (CNB) equivalent is =< 0.65.

Full Title of Study: “A Clinical Study to Characterize Baseline Biomarker Variability in Participants With Hepatocellular Carcinoma for Utilization of Target Engagement and Pharmacodynamic Biomarkers in Future Phase I Trials”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Diagnostic
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 2012

Interventions

  • Procedure: MRI
    • Participants undergo volumetric & diffusion weighted (DW) MRI. Participants are scanned twice, with an intervening fifteen minute walk between the scans.
  • Procedure: Pathology
    • Participants who are undergoing surgical resection of HCC per their standard of care treatment, will submit tumor samples for biomarker analysis.
  • Procedure: Blood Samples
    • Blood is collected from participants during screening Visit 1 – 24.5 ml. During Visit 3, blood samples totaling 22 ml, are collected at least 6-18 hours post-resection, and every other day up to a week until discharge. At follow up Visit 4, 5.5 ml of blood is collected.
  • Procedure: Blood Samples
    • Blood is collected from participants during screening Visit 1 – 24.5 ml, and follow up Visit 4 – 5.5 ml.

Arms, Groups and Cohorts

  • Experimental: Imaging
    • Magnetic resonance imaging (MRI) of HCC tumor.
  • Experimental: Pathology
    • Pathology samples from surgical resection of HCC tumor and adjacent liver.
  • Experimental: Imaging/Pathology
    • MRI of HCC tumor, followed by pathology samples from surgical resection of HCC tumor and adjacent liver.

Clinical Trial Outcome Measures

Primary Measures

  • Expression Levels of Beta-catenin mRNA From Core Needle Biopsy (CNB) Equivalents of Resected HCC.
    • Time Frame: Visit 3, approximately 7 days after screening Visit 1.
    • Resected tumors were fixed with formalin in paraffin embedded (FFPE) blocks, which were used to prepare multiple serial slide sections. The sections were to be analyzed for beta-catenin messenger RNA (mRNA) by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
  • Expression Levels of Beta-catenin Protein From Core Needle Biopsy (CNB) Equivalents of Resected HCC.
    • Time Frame: Visit 3, approximately 7 days after screening Visit 1.
    • Resected tumors were fixed in FFPE blocks, which were used to prepare multiple serial slide sections. The sections were to be analyzed for beta-catenin protein by automated image analysis.

Secondary Measures

  • Tumor Volumes From Repeated MRI Measurements of HCC.
    • Time Frame: Visit 2, approximately 7 days after screening Visit 1.
    • Two volumetric MRI and diffusion weighted (DW) MRI scans were performed without contrast on each participant. The two scans were separated by 10 to 15 minutes, and each scan was read by a separate reader to determine the volume of each tumor. The mean of log tumor volume is presented, based on tumors as observation units.
  • Median Apparent Diffusion Coefficient (Median ADC) of Tumors From Repeated MRI Measurements of HCC.
    • Time Frame: Visit 2, approximately 7 days after screening Visit 1.
    • Two volumetric MRI and diffusion weighted (DW) MRI scans were performed without contrast on each participant. The two scans were separated by 10 to 15 minutes, and each scan was read by a separate reader to derive a Median ADC for each tumor. The mean of the Median ADCs is presented based on tumours as observation units.
  • Expression Levels of Beta-catenin mRNA From CNB Equivalents of Liver Adjacent to HCC.
    • Time Frame: Visit 3, approximately 7 days after screening Visit 1.
    • Tissues adjacent to resected tumors were fixed in FFPE blocks, which were used to prepare multiple serial slide sections. The sections were to be analyzed for beta-catenin mRNA by qRT-PCR.
  • Expression Levels of Beta-catenin Protein From CNB Equivalents of Liver Adjacent to HCC.
    • Time Frame: Visit 3, approximately 7 days after screening Visit 1.
    • Tissues adjacent to resected tumors were fixed in FFPE blocks, which were used to prepare multiple serial slide sections. The sections were to be analyzed for beta-catenin protein by automated image analysis.
  • Expression Levels of Low Density Lipoprotein Receptor (LDL-R) in Resected HCC and Adjacent Liver From Whole Tissue Sections.
    • Time Frame: Visit 3, approximately 7 days after screening Visit 1.
    • Resected tumors and adjacent tissues were fixed in FFPE blocks, which were used to prepare multiple serial slide sections. The sections were to be analyzed for LDL-R protein by automated image analysis.

Participating in This Clinical Trial

Inclusion Criteria

  • Diagnosed with HCC. – Candidate for surgical resection or has no contraindications to MRI procedures. Exclusion Criteria:

  • Prior loco-regional treatment of tumor, unless there is untreated tumor present representing a distinct untreated nodule. – Confirmed or suspected diagnosis of fibrolamellar HCC, mixed HCC/cholangiocarcinoma or metastatic tumor. – Had a liver transplant.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Merck Sharp & Dohme LLC
  • Provider of Information About this Clinical Study
    • Sponsor

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