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

October 30, 2015 updated by: Merck Sharp & Dohme LLC

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
Visit 3, approximately 7 days after screening Visit 1.
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.
Visit 3, approximately 7 days after screening Visit 1.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Visit 2, approximately 7 days after screening Visit 1.
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.
Visit 2, approximately 7 days after screening Visit 1.
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.
Visit 3, approximately 7 days after screening Visit 1.
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.
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.
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.
Visit 3, approximately 7 days after screening Visit 1.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2012

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 16, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 31, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 1, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0000-215

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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