Hepatocellular Carcinoma
Conditions
Keywords
hepatocellular carcinoma, MRI, pharmacogenomics, beta-catenin
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.
Interventions
PROCEDUREMRI
Participants undergo volumetric & diffusion weighted (DW) MRI. Participants are scanned twice, with an intervening fifteen minute walk between the scans.
PROCEDUREPathology
Participants who are undergoing surgical resection of HCC per their standard of care treatment, will submit tumor samples for biomarker analysis.
PROCEDUREBlood 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.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Expression Levels of Beta-catenin mRNA From Core Needle Biopsy (CNB) Equivalents of Resected HCC. | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expression Levels of Beta-catenin mRNA From CNB Equivalents of Liver Adjacent to HCC. | 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. |
| Tumor Volumes From Repeated MRI Measurements of HCC. | 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. |
| Expression Levels of Low Density Lipoprotein Receptor (LDL-R) in Resected HCC and Adjacent Liver From Whole Tissue Sections. | 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. |
| Expression Levels of Beta-catenin Protein From CNB Equivalents of Liver Adjacent to HCC. | 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. |
| Median Apparent Diffusion Coefficient (Median ADC) of Tumors From Repeated MRI Measurements of HCC. | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants who enrolled in the study | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 61.4 Years STANDARD_DEVIATION 14.43 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 9 | 0 / 1 | 0 / 2 |
Outcome results
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).
Time frame: Visit 3, approximately 7 days after screening Visit 1.
Population: Due to early termination of the study, the low number of samples were not assayed and efficacy analyses were not performed.
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.
Time frame: Visit 3, approximately 7 days after screening Visit 1.
Population: Due to early termination of the study, the low number of samples were not assayed and efficacy analyses were not performed.
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.
Time frame: Visit 3, approximately 7 days after screening Visit 1.
Population: Due to early termination of the study, the low number of samples were not assayed and efficacy analyses were not performed.
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.
Time frame: Visit 3, approximately 7 days after screening Visit 1.
Population: Due to early termination of the study, the low number of samples were not assayed and efficacy analyses were not performed.
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.
Time frame: Visit 3, approximately 7 days after screening Visit 1.
Population: Due to early termination of the study, the low number of samples were not assayed and efficacy analyses were not performed.
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.
Time frame: Visit 2, approximately 7 days after screening Visit 1.
Population: Eleven participants underwent MRI and DW MRI scans and only eight of their tumors were deemed measurable by both readers for analysis. Participants in both the Imaging and Imaging/Pathology treatment groups were combined for this analysis, whereas participants in the Pathology only treatment group were not analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imaging | Median Apparent Diffusion Coefficient (Median ADC) of Tumors From Repeated MRI Measurements of HCC. | 1340.56 um^2/s | Standard Deviation 64.45 |
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.
Time frame: Visit 2, approximately 7 days after screening Visit 1.
Population: Eleven participants underwent MRI and DW MRI scans and only ten of their tumors were deemed measurable by both readers for analysis. Participants in both the Imaging and Imaging/Pathology treatment groups were combined for this analysis, whereas participants in the Pathology only treatment group were not analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imaging | Tumor Volumes From Repeated MRI Measurements of HCC. | 3.38 log cm^3 | Standard Deviation 0.235 |