Clinical trial NCT01871545: Evaluation of Liver Cancer With Magnetic Resonance Imaging (MRI)
Official title: Evaluation of HCC Response to Systemic Therapy With Quantitative MRI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatocellular Carcinoma
HCC
Keywords: hepatocellular carcinoma
HCC
liver cancer
liver disease
magnetic resonance imaging
MRI
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2013-06-06
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The incidence of hepatocellular carcinoma (HCC) has recently increased in the United States. Although imaging plays a major role in HCC screening and staging, the possibility of predicting HCC tumor grade, aggressiveness, angiogenesis and hypoxia with imaging are unmet needs. In addition, new antiangiogenic drugs now available to treat advanced HCC necessitate the use of new imaging criteria beyond size. The investigators would like to develop and validate non-invasive magnetic resonance imaging (MRI) methods based on advanced diffusion-weighted imaging (DWI), MR Elastography, BOLD (blood oxygen level dependent) MRI and perfusion-weighted imaging (PWI, using gadolinium contrast) to be used as non-invasive markers of major histopathologic features of HCC, and to predict and assess early response of HCC to systemic therapy. The investigators also would like to develop quality control tools to improve the quality and decrease variability of quantitative MRI metrics. These techniques combined could represent non-invasive correlates of histologic findings in HCC, could enable individualized therapy, and provide prognosis in patients with HCC.

Detailed description: The incidence of hepatocellular carcinoma (HCC) has recently increased in the US mostly due to an increase in chronic hepatitis C infection. Angiogenesis is critical for the growth and metastatic progression of HCC. With the development of new antiangiogenic drugs such as sorafenib, imaging methods to predict and assess therapeutic response beyond changes in size become critical. However, validated imaging methods to predict and assess early HCC response to targeted agents are lacking.

In this study, the investigators would like to develop quantitative MRI methods interrogating different features of HCC tumor biology and pathology, including tumor cellularity, grade, angiogenesis and hypoxia. The investigators propose a multiparametric approach combining advanced DWI (IVIM: intravoxel incoherent motion diffusion measuring perfusion fraction and true diffusion coefficient), DCE-MRI (dynamic contrast-enhanced MRI, which measures arterial and portal flow, mean transit time, blood volume and distribution volume), and BOLD MRI using oxygen or carbogen challenge. This protocol will be performed in patients with HCC undergoing hepatic resection. Routine and advanced histopathologic methods will be performed (tumor grade, CK19 expression, presence of microvascular invasion, VEGF expression, microvessel density, HIF 1-alpha expression). MRI metrics will be correlated with histopathologic metrics.

The first portion of the proposal involves the development of a QC algorithm assessing MR data quality and test-retest. The investigators will propose solutions to improve data acquisition and processing. The last 2 years of the study will be dedicated to a prospective randomized study comparing Yttrium 90 radioembolization to sorafenib, assessing the role of baseline MRI metrics and early changes (at 2 weeks) in these metrics as markers of tumor response and time to progression in patients with unresectable HCC.

Eligibility criteria: Inclusion Criteria:

Study group

* Patients diagnosed with HCC, who will undergo resection or transplantation within 6 months, as part of routine clinical care and patients diagnosed with unresectable HCC
* 18 years of age and older
* Patient is able to give informed consent for this study

Control group

* Healthy volunteers 18 years of age and older
* Subject is able to give informed consent for this study

Exclusion Criteria:

* Age less than 18 years
* Unable or unwilling to give informed consent
* Contra-indications to MRI:

  1. Electrical implants such as cardiac pacemakers or perfusion pumps
  2. Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants
  3. Ferromagnetic objects such as jewelry or metal clips in clothing
  4. Pregnant subjects
  5. Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions

Primary outcomes:
measure: SubStudy 1: Apparent Diffusion Coefficient (ADC)
timeFrame: Day 1
measure: SubStudy 1: Total Tumor Perfusion (Ft)
timeFrame: Day 1
measure: SubStudy 1: Tumor Arterial Perfusion Fraction (ART)
timeFrame: Day 1
measure: SubStudy 1: Tumor Mean Transit Time (MTT)
timeFrame: Day 1
measure: SubStudy 1: Tumor Distribution Volume (DV)
timeFrame: Day 1
measure: SubStudy 1: Oxygen Uptake
timeFrame: Day 1
measure: SubStudy 1: Percent Change in Oxygen Uptake
timeFrame: Day 1, pre-oxygen administration and 10 min. post-oxygen administration
measure: SubStudy 2: ADC
timeFrame: baseline and 6 weeks after Y90
measure: SubStudy 2: Diffusion Coefficient D
timeFrame: baseline and 6 weeks after Y90
measure: SubStudy 2: Pseudodiffusion Coefficient D*
timeFrame: baseline and 6 weeks after Y90
measure: SubStudy 2: Perfusion Fraction (PF)
timeFrame: baseline and 6 weeks after Y90
Secondary outcomes:
measure: SubStudy 2: Total Tumor Perfusion (Ft)
timeFrame: baseline and 6 weeks after Y90
measure: SubStudy 2: Tumor Arterial Perfusion Fraction (ART)
timeFrame: baseline and 6 weeks after Y90
measure: SubStudy 2: Tumor Mean Transit Time (MTT) of Contrast Agent
timeFrame: baseline and 6 weeks after Y90
measure: SubStudy 2: Extravascular Extracellular Volume ve
timeFrame: baseline and 6 weeks after Y90
measure: Substudy 2: Tumor Stiffness
timeFrame: baseline and 6 weeks after Y90
measure: Tumor Response
timeFrame: 6 weeks and 6-12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Bachir Taouli, MD
role: PRINCIPAL_INVESTIGATOR
References: