Trial Outcomes & Findings for 3-Tesla MRI Response to TACE in HCC (Liver Cancer) (NCT NCT02057874)

NCT ID: NCT02057874

Last Updated: 2018-07-11

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 2 participants
• Primary outcome timeframe: Baseline to up to 12 weeks post-TACE
• Results posted on: 2018-07-11

Participant Flow

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.

Participant milestones

Measure	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.
Overall Study STARTED	2
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

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.

Overall Study participant did not return for scan

1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Diagnostic (3T MRI) n=2 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	60 years STANDARD_DEVIATION 3 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to up to 12 weeks post-TACE

Population: Due to loss of funding data were not collected

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to up to 6 months post-TACE

Population: Due to loss of funding data were not collected

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to up to 12 weeks post-TACE

Population: Due to loss of funding data were not collected

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Subset of patients undergoing OLT: within 12 hours following surgery

Population: Due to loss of funding data were not collected

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to up to 6 months post-TACE

Population: Due to loss of funding data were not collected

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.

Outcome measures

Outcome data not reported

Adverse Events

Diagnostic (3T MRI)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Professor of Surgery and Cancer Biology

Vanderbilt University Medical Center

Phone: 615-936-2956

Email: lee.gorden@vanderbilt.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place