Adult Primary Hepatocellular CarcinomaNCT02057874
3-Tesla MRI Response to TACE in HCC (Liver Cancer)
A study testing 3 Tesla Magnetic Resonance Imaging and Magnevist® (Intravenous (IV) administration of MRI contrast agent) in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Resectable Adult Primary Liver Cancer
- What is being tested?
- 3 Tesla Magnetic Resonance Imaging and Magnevist® (Intravenous (IV) administration of MRI contrast agent)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to 4 Dec 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
Official title: Multi-Parametric 3 Tesla Magnetic Resonance Imaging (MRI) of Response to Transarterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma (HCC)
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.
- Conditions
- 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)
- Being tested
- 3 Tesla Magnetic Resonance Imaging, Magnevist® (Intravenous (IV) administration of MRI contrast agent)
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3 Tesla Magnetic Resonance ImagingDevice
Also called 3 Tesla MRI, 3T MRI (Philips Achieva), multi-parametric 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)Drug
Also called intravenous (IV) injection of Magnevist® (gadopentetate dimeglumine); IV contrast infusion; IV gadolinium (Gd)
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: 3 Tesla Magnetic Resonance Imaging; Drug: Magnevist® (Intravenous (IV) administration of MRI contrast agent) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to up to 12 weeks post-TACE
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to up to 6 months post-TACE
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2014 (estimated)
- Study startFeb 2014
- Primary completion19 Nov 2015
- Study completion4 Dec 2015
Why it stopped: Funding unavailable
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Primary Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, David Lee Gorden, Vanderbilt-Ingram Cancer Center
- Investigators
- David L Gorden, MD, Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02057874
- Sponsor's protocol ID
- VICC GI 1343
- Status last verified
- Jul 2018
- First submitted
- 5 Feb 2014
- Last updated
- 11 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Parametric 3 Tesla Magnetic Resonance Imaging (MRI) of Response to Transarterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT02057874
- Acronym / sponsor ID
- VICC GI 1343
- Conditions
- 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)
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding unavailable
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2014
- Primary completion
- 19 Nov 2015 (actual)
- Study completion
- 4 Dec 2015 (actual)
- First posted
- 7 Feb 2014 (estimated)
- Results
- Posted 11 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Diagnostic (3T MRI) | Experimental | Device: 3 Tesla Magnetic Resonance Imaging, Drug: Magnevist® (Intravenous (IV) administration of MRI contrast agent)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3 Tesla Magnetic Resonance ImagingAlso: 3 Tesla MRI, 3T MRI (Philips Achieva), multi-parametric imaging3T 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. | Device | Diagnostic (3T MRI) |
| Magnevist® (Intravenous (IV) administration of MRI contrast agent)Also: intravenous (IV) injection of Magnevist® (gadopentetate dimeglumine); IV contrast infusion; IV gadolinium (Gd)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. | Drug | Diagnostic (3T MRI) |
Primary outcome
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.
4 secondary outcomes
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Vanderbilt-Ingram Cancer Center, Find a Clinical TrialLink provided by the sponsor.
Related trials for Adult Primary Hepatocellular Carcinoma
Not yet recruitingPhase 1
Study of ACC-1898 in Adult Participants With Advanced Solid Tumors
Hepatocellular Carcinoma, Renal Cell Carcinoma
Active, not recruitingPhase 1
Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy
Adult Solid Neoplasm, Bladder Carcinoma
RecruitingPhase 1/2
First in Human Study to Evaluate AZD9793 in Participants With Advanced or Metastatic Solid Tumours
Hepatocellular Carcinoma
RecruitingPhase 1
Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations
Metastatic Hepatocellular Carcinoma, Solid Tumors
RecruitingPhase 1
Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Select Advanced Solid Tumor Indications Receiving Intravenous (IV) ABBV-400
Hepatocellular Carcinoma, Pancreatic Ductal Adenocarcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David L Gorden, MD principal investigator
Vanderbilt-Ingram Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 3 Tesla Magnetic Resonance Imaging and Magnevist® (Intravenous (IV) administration of MRI contrast agent) in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2018.