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

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

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.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: MRI; Procedure: Blood Samples; Procedure: Blood Samples; Procedure: Pathology

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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. 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.
EXPERIMENTAL: Pathology; Pathology samples from surgical resection of HCC tumor and adjacent liver.	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.; Procedure: Pathology; Participants who are undergoing surgical resection of HCC per their standard of care treatment, will submit tumor samples for biomarker analysis.
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: 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.; Procedure: Pathology; Participants who are undergoing surgical resection of HCC per their standard of care treatment, will submit tumor samples for biomarker analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Visit 3, approximately 7 days after screening Visit 1.
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.	Visit 3, approximately 7 days after screening Visit 1.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Visit 2, approximately 7 days after screening Visit 1.
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.	Visit 2, approximately 7 days after screening Visit 1.
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.	Visit 3, approximately 7 days after screening Visit 1.
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.	Visit 3, approximately 7 days after screening Visit 1.
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.	Visit 3, approximately 7 days after screening Visit 1.

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): September 1, 2012
• Study Completion (ACTUAL): November 1, 2012

Study Registration Dates

• First Submitted: December 16, 2011
• First Submitted That Met QC Criteria: January 26, 2012
• First Posted (ESTIMATE): January 31, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 1, 2015
• Last Update Submitted That Met QC Criteria: October 30, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: MRI; hepatocellular carcinoma; pharmacogenomics; beta-catenin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: 0000-215