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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01521780
First received: December 16, 2011
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Procedure: MRI
Procedure: Pathology
Procedure: Blood Samples
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome 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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Tumor Volumes From Repeated MRI Measurements of HCC. [ Time Frame: Visit 2, approximately 7 days after screening Visit 1. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 12
Study Start Date: April 2012
Study Completion Date: November 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imaging
Magnetic resonance imaging (MRI) of HCC tumor.
Procedure: MRI
Participants undergo volumetric & diffusion weighted (DW) MRI. Participants are scanned twice, with an intervening fifteen minute walk between the scans.
Procedure: Blood Samples
Blood is collected from participants during screening Visit 1 - 24.5 ml, and follow up Visit 4 - 5.5 ml.
Experimental: Pathology
Pathology samples from surgical resection of HCC tumor and adjacent liver.
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.
Experimental: Imaging/Pathology
MRI of HCC tumor, followed by pathology samples from surgical resection of HCC tumor and adjacent liver.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01521780     History of Changes
Other Study ID Numbers: 0000-215
Study First Received: December 16, 2011
Results First Received: August 14, 2013
Last Updated: July 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Merck Sharp & Dohme Corp.:
hepatocellular carcinoma
MRI
pharmacogenomics
beta-catenin

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on October 29, 2014