Not provided
Not provided
Not provided
Not provided
Not provided
Funding unavailable
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This pilot clinical trial examines how well different imaging biomarkers acquired using 3-Telsa magnetic resonance imaging (MRI) methods perform in determining treatment response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma. Compared to conventional imaging, multi-parametric 3-Tesla MRI offers the ability to quantitatively measure tissue structural, functional, cellular, and molecular properties, providing a more robust, clinically relevant method for assessing cancer response to therapy.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diagnostic (3T MRI) | Experimental | Patients undergo 3T MRI at baseline (=< 2 weeks before TACE) and at 2-4 weeks, 4-8 weeks, and 12 weeks after TACE. Each 3T MRI session will utilize a sequence of the following modalities: CEST-MRI, MT-MRI, DW-MRI, and DCE-MRI. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3 Tesla Magnetic Resonance Imaging | Device | 3T MRI consists of a series of radiofrequency (RF) pulse sequences optimized for acquiring CEST-, MT-, DW-, and DCE-MRI data in one seamless imaging examination. For DCE, MR contrast agent will be intravenously administered. |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of Changes in Imaging Biomarkers (Ktrans, ADC, MTR, and APTasym) as Measured by DCE-, DW-, MT-, and CEST-MRI at 3 Tesla, Respectively, With Changes in Tumor Volume (mRECIST). | The following will be longitudinally measured using 3 Tesla (3T) magnetic resonance imaging (MRI) prior to transarterial chemoembolization (TACE) and 2-4, 4-8, and 12 weeks following TACE: 1) the volume transfer coefficient (Ktrans), measured by dynamic contrast-enhanced (DCE) MRI; 2) the apparent diffusion coefficient (ADC), measured by diffusion-weighted (DW) MRI; 3) the magnetization transfer ratio (MTR), measured by magnetization transfer (MT) MRI; and 4) the amide proton transfer asymmetry (APTasym), measured by chemical exchange saturation transfer (CEST) MRI. We will use a general linear model (GLM) approach to measure the association between changes in each of the above imaging metrics (relative to pretreatment baseline) and changes in tumor volume (according to standard-of-care modified RECIST) at 3 or 6 month follow-up, accounting for the effect of potential confounders, e.g., age and size of the tumor at baseline. | Baseline to up to 12 weeks post-TACE |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of Changes in Ktrans, ADC, MTR, and APTasym (Measured by DCE-, DW-, MT-, and CEST-MRI at 3 Tesla, Respectively) With Time-to-progression (TTP). | Proportional hazard model will be employed to assess the ability of the longitudinal change (relative to pretreatment baseline) in each of the 3T MR imaging metrics (Ktrans, ADC, MTR, and APTasym) to predict patient survival outcomes, time-to-progression (TTP) and progression-free survival (PFS) as well as overall survival (OS). The calibration of prediction will be validated by computing the difference between predicted survival and Kaplan-Meier survival estimates at a fixed time, which estimates the over-optimism of the difference using bootstrapping. |
Not provided
Inclusion Criteria:
Subjects must have signed an institutional review board (IRB)-approved informed consent document
Subjects must have verified unresectable hepatocellular carcinoma (HCC), diagnosed on the basis of clinical and imaging criteria
Subjects must be classified as TNM stage I, II, or III; alternatively, subjects may be classified as Barcelona Clinic Liver Cancer (BCLC) stage A or B
Subjects must be scheduled to undergo transarterial chemoembolization (TACE)
Subjects must have at least 1 lesion being targeted by TACE that is > 2 cm in the longest cross-sectional (axial plane) diameter
Subjects must satisfy one of the following conditions pertaining to their eligibility to undergo orthotopic liver transplantation (OLT):
Exclusion Criteria:
Subjects who have received prior treatment for HCC (prior surgical procedures not related to HCC are allowed)
Subjects who have undergone prior radioembolization
Subjects with a central venous line
Subjects who have any type of biomedical implant, device and/or ferromagnetic material that can be displaced, perturbed, or otherwise malfunction due to mechanical, electronic, or magnetic means; these items may include:
Creatinine >= 1.5 times upper limit of normal
Estimated glomerular filtration rate (eGFR) < 30 mL/min
Subjects who are pregnant or nursing
Subjects who have had past allergic or other adverse reactions to intravenous injection of Magnevist® (gadopentetate dimeglumine) or other gadolinium-containing contrast agents
Subjects who exhibit noticeable anxiety, claustrophobia, or vertigo when moved into the scanner
Subjects incapable of giving informed written consent, for the following reasons:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| David L Gorden, MD | Vanderbilt-Ingram Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | 37232 | United States |
Not provided
| Label | URL |
|---|---|
| Vanderbilt-Ingram Cancer Center, Find a Clinical Trial | View source |
Not provided
Not provided
Participants were recruited to this trial at Vanderbilt University Medical Center from 02/06/2014 to 11/19/2015. The study closed prematurely due to a loss of funding.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Diagnostic (3T MRI) | Patients undergo 3T MRI at baseline (=< 2 weeks before TACE) and at 2-4 weeks, 4-8 weeks, and 12 weeks after TACE. Each 3T MRI session will utilize a sequence of the following modalities: CEST-MRI, MT-MRI, DW-MRI, and DCE-MRI. 3 Tesla Magnetic Resonance Imaging: 3T MRI consists of a series of radiofrequency (RF) pulse sequences optimized for acquiring CEST-, MT-, DW-, and DCE-MRI data in one seamless imaging examination. For DCE, MR contrast agent will be intravenously administered. Magnevist® (Intravenous (IV) administration of MRI contrast agent): For the acquisition of DCE-MR data, the FDA-approved contrast agent Magnevist® (gadopentetate dimeglumine, 0.1 mmol/kg) will be delivered intravenously by the MR technologist at a rate of 2 mL/sec (followed by a saline flush) via a power injector after the acquisition of a set of baseline dynamic scans. The entire sequence lasts approximately 8 minutes. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Magnevist® (Intravenous (IV) administration of MRI contrast agent) | Drug | For the acquisition of DCE-MR data, the FDA-approved contrast agent Magnevist® (gadopentetate dimeglumine, 0.1 mmol/kg) will be delivered intravenously by the MR technologist at a rate of 2 mL/sec (followed by a saline flush) via a power injector after the acquisition of a set of baseline dynamic scans. The entire sequence lasts approximately 8 minutes. |
|
|
| Baseline to up to 6 months post-TACE |
| Correlation of Changes in Ktrans, ADC, MTR, and APTasym (Measured by DCE-, DW-, MT-, and CEST-MRI at 3 Tesla, Respectively) With Changes in the Ratio of Viable-to-necrotic Tumor Volume | Longitudinal changes in 3T MRI-derived measures and the change in the ratio of viable vs. necrotic tumor will be assessed by using a GLM approach in which the underlying temporal correlation can be modeled via an autoregressive order one (AR(1)) structure, validated by computing Akaike Information Criterion (AIC) against the other common structures, e.g., unstructured and constant correlation. | Baseline to up to 12 weeks post-TACE |
| Correlation of Ktrans, ADC, MTR, and APTasym (Measured by DCE-, DW-, MT-, and CEST-MRI at 3 Tesla, Respectively) With Pathological Response Within Explanted Tissue Following Orthotopic Liver Transplant (OLT) | Histopathological features on explanted livers following OLT, including percentage necrosis and cellular density as determined by hematoxylin and eosin staining, as well as the extent of fibrosis as determined by collagen staining, will be assessed for correspondence with findings on ex vivo 3T MRI. | Subset of patients undergoing OLT: within 12 hours following surgery |
| Correlation of Changes in Ktrans, ADC, MTR, and APTasym (Measured by DCE-, DW-, MT-, and CEST-MRI at 3 Tesla, Respectively) With Overall Survival (OS) | Proportional hazard model will be employed to assess the ability of the longitudinal change (relative to pretreatment baseline) in each of the 3T MR imaging metrics (Ktrans, ADC, MTR, and APTasym) to predict patient survival outcomes, time-to-progression (TTP) and progression-free survival (PFS) as well as overall survival (OS). The calibration of prediction will be validated by computing the difference between predicted survival and Kaplan-Meier survival estimates at a fixed time, which estimates the over-optimism of the difference using bootstrapping. | Baseline to up to 6 months post-TACE |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Diagnostic (3T MRI) | Patients undergo 3T MRI at baseline (=< 2 weeks before TACE) and at 2-4 weeks, 4-8 weeks, and 12 weeks after TACE. Each 3T MRI session will utilize a sequence of the following modalities: CEST-MRI, MT-MRI, DW-MRI, and DCE-MRI. 3 Tesla Magnetic Resonance Imaging: 3T MRI consists of a series of radiofrequency (RF) pulse sequences optimized for acquiring CEST-, MT-, DW-, and DCE-MRI data in one seamless imaging examination. For DCE, MR contrast agent will be intravenously administered. Magnevist® (Intravenous (IV) administration of MRI contrast agent): For the acquisition of DCE-MR data, the FDA-approved contrast agent Magnevist® (gadopentetate dimeglumine, 0.1 mmol/kg) will be delivered intravenously by the MR technologist at a rate of 2 mL/sec (followed by a saline flush) via a power injector after the acquisition of a set of baseline dynamic scans. The entire sequence lasts approximately 8 minutes. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Correlation of Changes in Imaging Biomarkers (Ktrans, ADC, MTR, and APTasym) as Measured by DCE-, DW-, MT-, and CEST-MRI at 3 Tesla, Respectively, With Changes in Tumor Volume (mRECIST). | The following will be longitudinally measured using 3 Tesla (3T) magnetic resonance imaging (MRI) prior to transarterial chemoembolization (TACE) and 2-4, 4-8, and 12 weeks following TACE: 1) the volume transfer coefficient (Ktrans), measured by dynamic contrast-enhanced (DCE) MRI; 2) the apparent diffusion coefficient (ADC), measured by diffusion-weighted (DW) MRI; 3) the magnetization transfer ratio (MTR), measured by magnetization transfer (MT) MRI; and 4) the amide proton transfer asymmetry (APTasym), measured by chemical exchange saturation transfer (CEST) MRI. We will use a general linear model (GLM) approach to measure the association between changes in each of the above imaging metrics (relative to pretreatment baseline) and changes in tumor volume (according to standard-of-care modified RECIST) at 3 or 6 month follow-up, accounting for the effect of potential confounders, e.g., age and size of the tumor at baseline. | Due to loss of funding data were not collected | Posted | Baseline to up to 12 weeks post-TACE |
|
| |||||||||||||||||||
| Secondary | Correlation of Changes in Ktrans, ADC, MTR, and APTasym (Measured by DCE-, DW-, MT-, and CEST-MRI at 3 Tesla, Respectively) With Time-to-progression (TTP). | Proportional hazard model will be employed to assess the ability of the longitudinal change (relative to pretreatment baseline) in each of the 3T MR imaging metrics (Ktrans, ADC, MTR, and APTasym) to predict patient survival outcomes, time-to-progression (TTP) and progression-free survival (PFS) as well as overall survival (OS). The calibration of prediction will be validated by computing the difference between predicted survival and Kaplan-Meier survival estimates at a fixed time, which estimates the over-optimism of the difference using bootstrapping. | Due to loss of funding data were not collected | Posted | Baseline to up to 6 months post-TACE |
|
| |||||||||||||||||||
| Secondary | Correlation of Changes in Ktrans, ADC, MTR, and APTasym (Measured by DCE-, DW-, MT-, and CEST-MRI at 3 Tesla, Respectively) With Changes in the Ratio of Viable-to-necrotic Tumor Volume | Longitudinal changes in 3T MRI-derived measures and the change in the ratio of viable vs. necrotic tumor will be assessed by using a GLM approach in which the underlying temporal correlation can be modeled via an autoregressive order one (AR(1)) structure, validated by computing Akaike Information Criterion (AIC) against the other common structures, e.g., unstructured and constant correlation. | Due to loss of funding data were not collected | Posted | Baseline to up to 12 weeks post-TACE |
|
| |||||||||||||||||||
| Secondary | Correlation of Ktrans, ADC, MTR, and APTasym (Measured by DCE-, DW-, MT-, and CEST-MRI at 3 Tesla, Respectively) With Pathological Response Within Explanted Tissue Following Orthotopic Liver Transplant (OLT) | Histopathological features on explanted livers following OLT, including percentage necrosis and cellular density as determined by hematoxylin and eosin staining, as well as the extent of fibrosis as determined by collagen staining, will be assessed for correspondence with findings on ex vivo 3T MRI. | Due to loss of funding data were not collected | Posted | Subset of patients undergoing OLT: within 12 hours following surgery |
|
| |||||||||||||||||||
| Secondary | Correlation of Changes in Ktrans, ADC, MTR, and APTasym (Measured by DCE-, DW-, MT-, and CEST-MRI at 3 Tesla, Respectively) With Overall Survival (OS) | Proportional hazard model will be employed to assess the ability of the longitudinal change (relative to pretreatment baseline) in each of the 3T MR imaging metrics (Ktrans, ADC, MTR, and APTasym) to predict patient survival outcomes, time-to-progression (TTP) and progression-free survival (PFS) as well as overall survival (OS). The calibration of prediction will be validated by computing the difference between predicted survival and Kaplan-Meier survival estimates at a fixed time, which estimates the over-optimism of the difference using bootstrapping. | Due to loss of funding data were not collected | Posted | Baseline to up to 6 months post-TACE |
|
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Diagnostic (3T MRI) | Patients undergo 3T MRI at baseline (=< 2 weeks before TACE) and at 2-4 weeks, 4-8 weeks, and 12 weeks after TACE. Each 3T MRI session will utilize a sequence of the following modalities: CEST-MRI, MT-MRI, DW-MRI, and DCE-MRI. 3 Tesla Magnetic Resonance Imaging: 3T MRI consists of a series of radiofrequency (RF) pulse sequences optimized for acquiring CEST-, MT-, DW-, and DCE-MRI data in one seamless imaging examination. For DCE, MR contrast agent will be intravenously administered. Magnevist® (Intravenous (IV) administration of MRI contrast agent): For the acquisition of DCE-MR data, the FDA-approved contrast agent Magnevist® (gadopentetate dimeglumine, 0.1 mmol/kg) will be delivered intravenously by the MR technologist at a rate of 2 mL/sec (followed by a saline flush) via a power injector after the acquisition of a set of baseline dynamic scans. The entire sequence lasts approximately 8 minutes. | 0 | 2 | 0 | 2 | 0 | 2 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor of Surgery and Cancer Biology | Vanderbilt University Medical Center | 615-936-2956 | lee.gorden@vanderbilt.edu |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D019786 | Gadolinium DTPA |
| D005682 | Gadolinium |
| ID | Term |
|---|---|
| D004369 | Pentetic Acid |
| D011073 | Polyamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D000085 | Acetates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D056831 | Coordination Complexes |
| D028581 | Lanthanoid Series Elements |
| D008674 | Metals, Rare Earth |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D008670 | Metals |
Not provided
Not provided