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

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ClinicalTrials.gov Identifier: NCT01521780
Recruitment Status : Terminated
First Posted : January 31, 2012
Results First Posted : October 28, 2013
Last Update Posted : November 2, 2015
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE December 16, 2011
First Posted Date  ICMJE January 31, 2012
Results First Submitted Date  ICMJE August 14, 2013
Results First Posted Date  ICMJE October 28, 2013
Last Update Posted Date November 2, 2015
Study Start Date  ICMJE April 2012
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2013)
  • 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).
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2012)
  • 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. ]
  • 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. ]
Change History Complete list of historical versions of study NCT01521780 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2013)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2012)
  • Tumor Volumes From Repeated MRI Measurements of HCC. [ Time Frame: Visit 2, approximately 7 days after screening Visit 1. ]
  • Apparent diffusion coefficients (ADC) of tumors from repeated MRI measurements of HCC. [ Time Frame: 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. ]
  • 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. ]
  • 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. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Characterization of Baseline Biomarker Variability in Participants With Hepatocellular Carcinoma (MK-0000-215)
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Hepatocellular Carcinoma
Intervention  ICMJE
  • Procedure: MRI
    Participants undergo volumetric & diffusion weighted (DW) MRI. Participants are scanned twice, with an intervening fifteen minute walk between the scans.
  • Procedure: Pathology
    Participants who are undergoing surgical resection of HCC per their standard of care treatment, will submit tumor samples for biomarker analysis.
  • 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.
Study Arms  ICMJE
  • Experimental: Imaging
    Magnetic resonance imaging (MRI) of HCC tumor.
    Interventions:
    • Procedure: MRI
    • Procedure: Blood Samples
  • Experimental: Pathology
    Pathology samples from surgical resection of HCC tumor and adjacent liver.
    Interventions:
    • Procedure: Pathology
    • Procedure: Blood Samples
  • Experimental: Imaging/Pathology
    MRI of HCC tumor, followed by pathology samples from surgical resection of HCC tumor and adjacent liver.
    Interventions:
    • Procedure: MRI
    • Procedure: Pathology
    • Procedure: Blood Samples
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 13, 2012)
12
Original Estimated Enrollment  ICMJE
 (submitted: January 26, 2012)
40
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Taiwan,   United States
 
Administrative Information
NCT Number  ICMJE NCT01521780
Other Study ID Numbers  ICMJE 0000-215
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Merck Sharp & Dohme Corp.
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP