Back to resultsCharacterization of Baseline Biomarker Variability in Participants With Hepatocellular Carcinoma (MK-0000-215)
Primary Purpose
Hepatocellular Carcinoma
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MRI
Pathology
Blood Samples
Blood Samples
Sponsored by
About this trial
This is an interventional diagnostic trial for Hepatocellular Carcinoma focused on measuring hepatocellular carcinoma, MRI, pharmacogenomics, beta-catenin
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Imaging
Pathology
Imaging/Pathology
Arm Description
Magnetic resonance imaging (MRI) of HCC tumor.
Pathology samples from surgical resection of HCC tumor and adjacent liver.
MRI of HCC tumor, followed by pathology samples from surgical resection of HCC tumor and adjacent liver.
Outcomes
Primary Outcome Measures
Expression Levels of Beta-catenin mRNA From Core Needle Biopsy (CNB) Equivalents of Resected HCC.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01521780
First Posted
December 16, 2011
Last Updated
October 30, 2015
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01521780
Brief Title
Characterization of Baseline Biomarker Variability in Participants With Hepatocellular Carcinoma (MK-0000-215)
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Terminated
Study Start Date
April 2012 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
hepatocellular carcinoma, MRI, pharmacogenomics, beta-catenin
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Imaging
Arm Type
Experimental
Arm Description
Magnetic resonance imaging (MRI) of HCC tumor.
Arm Title
Pathology
Arm Type
Experimental
Arm Description
Pathology samples from surgical resection of HCC tumor and adjacent liver.
Arm Title
Imaging/Pathology
Arm Type
Experimental
Arm Description
MRI of HCC tumor, followed by pathology samples from surgical resection of HCC tumor and adjacent liver.
Intervention Type
Procedure
Intervention Name(s)
MRI
Intervention Description
Participants undergo volumetric & diffusion weighted (DW) MRI. Participants are scanned twice, with an intervening fifteen minute walk between the scans.
Intervention Type
Procedure
Intervention Name(s)
Pathology
Intervention Description
Participants who are undergoing surgical resection of HCC per their standard of care treatment, will submit tumor samples for biomarker analysis.
Intervention Type
Procedure
Intervention Name(s)
Blood Samples
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Blood Samples
Intervention Description
Blood is collected from participants during screening Visit 1 - 24.5 ml, and follow up Visit 4 - 5.5 ml.
Primary Outcome Measure Information:
Title
Expression Levels of Beta-catenin mRNA From Core Needle Biopsy (CNB) Equivalents of Resected HCC.
Description
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).
Time Frame
Visit 3, approximately 7 days after screening Visit 1.
Title
Expression Levels of Beta-catenin Protein From Core Needle Biopsy (CNB) Equivalents of Resected HCC.
Description
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.
Time Frame
Visit 3, approximately 7 days after screening Visit 1.
Secondary Outcome Measure Information:
Title
Tumor Volumes From Repeated MRI Measurements of HCC.
Description
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.
Time Frame
Visit 2, approximately 7 days after screening Visit 1.
Title
Median Apparent Diffusion Coefficient (Median ADC) of Tumors From Repeated MRI Measurements of HCC.
Description
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.
Time Frame
Visit 2, approximately 7 days after screening Visit 1.
Title
Expression Levels of Beta-catenin mRNA From CNB Equivalents of Liver Adjacent to HCC.
Description
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.
Time Frame
Visit 3, approximately 7 days after screening Visit 1.
Title
Expression Levels of Beta-catenin Protein From CNB Equivalents of Liver Adjacent to HCC.
Description
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.
Time Frame
Visit 3, approximately 7 days after screening Visit 1.
Title
Expression Levels of Low Density Lipoprotein Receptor (LDL-R) in Resected HCC and Adjacent Liver From Whole Tissue Sections.
Description
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.
Time Frame
Visit 3, approximately 7 days after screening Visit 1.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
12. IPD Sharing Statement
Learn more about this trial
Characterization of Baseline Biomarker Variability in Participants With Hepatocellular Carcinoma (MK-0000-215)
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