search
Back to results

3-Tesla MRI Response to TACE in HCC (Liver Cancer)

Primary Purpose

Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Resectable Adult Primary Liver Cancer

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
3 Tesla Magnetic Resonance Imaging
Magnevist® (Intravenous (IV) administration of MRI contrast agent)
Sponsored by
Vanderbilt-Ingram Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Adult Primary Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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):

    • HCC that is within Milan Criteria, i.e., TACE is indicated as a "bridge" to OLT (Group I); or
    • HCC that is outside Milan Criteria, i.e., TACE is indicated as a means of "down-staging" into transplant eligibility (Group II)

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:

    • Metallic fragments or shrapnel (such as from war wounds)
    • Cerebral aneurysm clips, biopsy marker clips
    • Vascular access ports (as are used with intravenous chemotherapy)
    • Cochlear implants, pacemakers, neurostimulators, biostimulators, and electronic infusion pumps **Implanted materials other than those verified as being rated "magnetic resonance [MR] Safe" or "MR Conditional 6" will not be allowed on study
  • 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:

    • Inability to adhere to the experimental protocols for any reason
    • Inability to communicate with the research team
    • Mental disability, altered mental status, confusion, or psychiatric disorders
    • Prisoners or others susceptible to coercion

Sites / Locations

  • Vanderbilt-Ingram Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic (3T MRI)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
February 5, 2014
Last Updated
July 10, 2018
Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT02057874
Brief Title
3-Tesla MRI Response to TACE in HCC (Liver Cancer)
Official Title
Multi-Parametric 3 Tesla Magnetic Resonance Imaging (MRI) of Response to Transarterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma (HCC)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Terminated
Why Stopped
Funding unavailable
Study Start Date
February 2014 (undefined)
Primary Completion Date
November 19, 2015 (Actual)
Study Completion Date
December 4, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Resectable Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Stage A Adult Primary Liver Cancer (BCLC), Stage B Adult Primary Liver Cancer (BCLC)

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Diagnostic (3T MRI)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
3 Tesla Magnetic Resonance Imaging
Other Intervention Name(s)
3 Tesla MRI, 3T MRI (Philips Achieva), multi-parametric imaging
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Magnevist® (Intravenous (IV) administration of MRI contrast agent)
Other Intervention Name(s)
intravenous (IV) injection of Magnevist® (gadopentetate dimeglumine); IV contrast infusion; IV gadolinium (Gd)
Intervention Description
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.
Primary Outcome Measure Information:
Title
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).
Description
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.
Time Frame
Baseline to up to 12 weeks post-TACE
Secondary Outcome Measure Information:
Title
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).
Description
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.
Time Frame
Baseline to up to 6 months post-TACE
Title
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
Description
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.
Time Frame
Baseline to up to 12 weeks post-TACE
Title
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)
Description
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.
Time Frame
Subset of patients undergoing OLT: within 12 hours following surgery
Title
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)
Description
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.
Time Frame
Baseline to up to 6 months post-TACE

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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): HCC that is within Milan Criteria, i.e., TACE is indicated as a "bridge" to OLT (Group I); or HCC that is outside Milan Criteria, i.e., TACE is indicated as a means of "down-staging" into transplant eligibility (Group II) 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: Metallic fragments or shrapnel (such as from war wounds) Cerebral aneurysm clips, biopsy marker clips Vascular access ports (as are used with intravenous chemotherapy) Cochlear implants, pacemakers, neurostimulators, biostimulators, and electronic infusion pumps **Implanted materials other than those verified as being rated "magnetic resonance [MR] Safe" or "MR Conditional 6" will not be allowed on study 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: Inability to adhere to the experimental protocols for any reason Inability to communicate with the research team Mental disability, altered mental status, confusion, or psychiatric disorders Prisoners or others susceptible to coercion
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David L Gorden, MD
Organizational Affiliation
Vanderbilt-Ingram Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.vicc.org/ct/
Description
Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

Learn more about this trial

3-Tesla MRI Response to TACE in HCC (Liver Cancer)

We'll reach out to this number within 24 hrs