Hepatocellular CarcinomaPhase 1NCT01521780
Characterization of Baseline Biomarker Variability in Participants With Hepatocellular Carcinoma (MK-0000-215)
A Phase 1 study testing MRI, Pathology and Blood Samples in people with Hepatocellular Carcinoma, run by Merck Sharp & Dohme LLC.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- MRI, Pathology and Blood Samples
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- Apr 2012to Nov 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with HCC.
- Candidate for surgical resection or has no contraindications to MRI procedures.
Who cannot join
- 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.
About this study
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
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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- MRI, Pathology, Blood Samples
- Keywords
- hepatocellular carcinoma, MRI, pharmacogenomics, beta-catenin
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIProcedure or surgery
Participants undergo volumetric \& diffusion weighted (DW) MRI. Participants are scanned twice, with an intervening fifteen minute walk between the scans.
PathologyProcedure or surgery
Participants who are undergoing surgical resection of HCC per their standard of care treatment, will submit tumor samples for biomarker analysis.
Blood SamplesProcedure or surgery
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 SamplesProcedure or surgery
Blood is collected from participants during screening Visit 1 - 24.5 ml, and follow up Visit 4 - 5.5 ml.
| Study group | Role | What they receive |
|---|---|---|
| Imaging | Experimental | Magnetic resonance imaging (MRI) of HCC tumor. Receives: Procedure: MRI; Procedure: Blood Samples |
| Pathology | Experimental | Pathology samples from surgical resection of HCC tumor and adjacent liver. Receives: Procedure: Pathology; Procedure: Blood Samples |
| Imaging/Pathology | Experimental | MRI of HCC tumor, followed by pathology samples from surgical resection of HCC tumor and adjacent liver. Receives: Procedure: MRI; Procedure: Pathology; Procedure: Blood Samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Visit 3, approximately 7 days after screening Visit 1.
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Visit 3, approximately 7 days after screening Visit 1.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2012 (estimated)
- Study startApr 2012
- Primary completionSep 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01521780
- Sponsor's protocol ID
- 0000-215
- Status last verified
- Oct 2015
- First submitted
- 16 Dec 2011
- Last updated
- 2 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01521780
- Acronym / sponsor ID
- 0000-215
- Conditions
- Hepatocellular Carcinoma
- Keywords
- hepatocellular carcinoma, MRI, pharmacogenomics, beta-catenin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Apr 2012
- Primary completion
- Sep 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 31 Jan 2012 (estimated)
- Results
- Posted 28 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Imaging | Experimental | Procedure: MRI, Procedure: Blood SamplesMagnetic resonance imaging (MRI) of HCC tumor. |
| Pathology | Experimental | Procedure: Pathology, Procedure: Blood SamplesPathology samples from surgical resection of HCC tumor and adjacent liver. |
| Imaging/Pathology | Experimental | Procedure: MRI, Procedure: Pathology, Procedure: Blood SamplesMRI of HCC tumor, followed by pathology samples from surgical resection of HCC tumor and adjacent liver. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnosed with HCC.
- Candidate for surgical resection or has no contraindications to MRI procedures.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRIParticipants undergo volumetric \& diffusion weighted (DW) MRI. Participants are scanned twice, with an intervening fifteen minute walk between the scans. | Procedure or surgery | Imaging, Imaging/Pathology |
| PathologyParticipants who are undergoing surgical resection of HCC per their standard of care treatment, will submit tumor samples for biomarker analysis. | Procedure or surgery | Imaging/Pathology, Pathology |
| Blood SamplesBlood 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 or surgery | Imaging/Pathology, Pathology |
| Blood SamplesBlood is collected from participants during screening Visit 1 - 24.5 ml, and follow up Visit 4 - 5.5 ml. | Procedure or surgery | Imaging |
Primary outcome
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.
5 secondary outcomes
Tumor Volumes From Repeated MRI Measurements of HCC.
Time frame: 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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hepatocellular Carcinoma
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MRI, Pathology and Blood Samples in people with Hepatocellular Carcinoma, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2015.