Trial record 4 of 603 for:    Open Studies | "Liver Neoplasms"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Vanderbilt-Ingram Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
David Lee Gorden, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT02057874
First received: February 5, 2014
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
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)
Device: 3 Tesla Magnetic Resonance Imaging
Drug: Magnevist® (Intravenous (IV) administration of MRI contrast agent)

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Multi-Parametric 3 Tesla Magnetic Resonance Imaging (MRI) of Response to Transarterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma (HCC)

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

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). [ Time Frame: Baseline to up to 12 weeks post-TACE ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline to up to 6 months post-TACE ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to up to 12 weeks post-TACE ] [ Designated as safety issue: No ]
    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) [ Time Frame: Subset of patients undergoing OLT: within 12 hours following surgery ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to up to 6 months post-TACE ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 38
Study Start Date: February 2014
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Device: 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.
Other Name: 3 Tesla MRI, 3T MRI (Philips Achieva), multi-parametric imaging
Drug: 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.
Other Name: intravenous (IV) injection of Magnevist® (gadopentetate dimeglumine); IV contrast infusion; IV gadolinium (Gd)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02057874

Contacts
Contact: VICC Clinical Trials Information Program 800-811-8480

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: VICC Clinical Trials Information Program    800-811-8480      
Principal Investigator: David L Gordon, MD         
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Principal Investigator: David L Gorden, MD Vanderbilt-Ingram Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: David Lee Gorden, Professor of Surgery (Hepatobiliary and Liver Transplantation), Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT02057874     History of Changes
Other Study ID Numbers: VICC GI 1343
Study First Received: February 5, 2014
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Contrast Media
Gadolinium DTPA
Gadobenic acid
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014