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

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ClinicalTrials.gov Identifier: NCT02057874
Recruitment Status : Terminated (Funding unavailable)
First Posted : February 7, 2014
Results First Posted : July 11, 2018
Last Update Posted : July 11, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
David Lee Gorden, Vanderbilt-Ingram Cancer Center

Tracking Information
First Submitted Date  ICMJE February 5, 2014
First Posted Date  ICMJE February 7, 2014
Results First Submitted Date  ICMJE April 12, 2018
Results First Posted Date  ICMJE July 11, 2018
Last Update Posted Date July 11, 2018
Study Start Date  ICMJE February 2014
Actual Primary Completion Date November 19, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 6, 2014)
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 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2014)
  • 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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 3-Tesla MRI Response to TACE in HCC (Liver Cancer)
Official Title  ICMJE Multi-Parametric 3 Tesla Magnetic Resonance Imaging (MRI) of Response to Transarterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma (HCC)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE
  • 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)
Intervention  ICMJE
  • 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)
Study Arms  ICMJE 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.
Interventions:
  • Device: 3 Tesla Magnetic Resonance Imaging
  • Drug: Magnevist® (Intravenous (IV) administration of MRI contrast agent)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 22, 2016)
2
Original Estimated Enrollment  ICMJE
 (submitted: February 6, 2014)
38
Actual Study Completion Date  ICMJE December 4, 2015
Actual Primary Completion Date November 19, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02057874
Other Study ID Numbers  ICMJE VICC GI 1343
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party David Lee Gorden, Vanderbilt-Ingram Cancer Center
Study Sponsor  ICMJE Vanderbilt-Ingram Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: David L Gorden, MD Vanderbilt-Ingram Cancer Center
PRS Account Vanderbilt-Ingram Cancer Center
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP