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

Phase 1

Terminated

• Conditions: Hepatocellular Carcinoma
• Interventions: Procedure: MRI; Procedure: Pathology; Procedure: Blood Samples

• Registration Number: NCT01521780
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-12-16
• Study First Submitted QC: 2012-01-26
• Study First Posted: 2012-01-31
• Study Start: 2012-04
• Primary Completion: 2012-09
• Study Completion: 2012-11
• Results First Submitted: 2013-08-14
• Results First Submitted QC: 2013-08-14
• Results First Posted: 2013-10-28
• Status Verified: 2015-10
• Last Update Submitted: 2015-10-30
• Last Update Posted: 2015-11-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Imaging	MRI	Magnetic resonance imaging (MRI) of HCC tumor.
Pathology	Pathology	Pathology samples from surgical resection of HCC tumor and adjacent liver.
Imaging/Pathology	MRI	MRI of HCC tumor, followed by pathology samples from surgical resection of HCC tumor and adjacent liver.
Imaging/Pathology	Pathology	MRI of HCC tumor, followed by pathology samples from surgical resection of HCC tumor and adjacent liver.
Imaging/Pathology	Blood Samples	MRI of HCC tumor, followed by pathology samples from surgical resection of HCC tumor and adjacent liver.
Pathology	Blood Samples	Pathology samples from surgical resection of HCC tumor and adjacent liver.
Imaging	Blood Samples	Magnetic resonance imaging (MRI) of HCC tumor.

Primary Outcome Measures

Name	Time	Method
Expression Levels of Beta-catenin mRNA From Core Needle Biopsy (CNB) Equivalents of Resected HCC.	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.	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 Outcome Measures

Name	Time	Method
Expression Levels of Beta-catenin mRNA From CNB Equivalents of Liver Adjacent to HCC.	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.	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.
Tumor Volumes From Repeated MRI Measurements of HCC.	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.	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 Low Density Lipoprotein Receptor (LDL-R) in Resected HCC and Adjacent Liver From Whole Tissue Sections.	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.