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

Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01521780
• Other study ID #: 0000-215
• Status: Terminated
• Phase: Phase 1
• First received: December 16, 2011
• Last updated: October 30, 2015
• Start date: April 2012
• Est. completion date: November 2012

Study information

• Verified date: October 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: November 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Procedure:
• MRI
Participants undergo volumetric & diffusion weighted (DW) MRI. Participants are scanned twice, with an intervening fifteen minute walk between the scans.
• Pathology
Participants who are undergoing surgical resection of HCC per their standard of care treatment, will submit tumor samples for biomarker analysis.
• 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.
• Blood Samples
Blood is collected from participants during screening Visit 1 - 24.5 ml, and follow up Visit 4 - 5.5 ml.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Primary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No