Overview: ACRIN 6690 will examine the diagnostic accuracy of CT and MRI to detect
hepatocellular carcinoma (HCC) in patients with chronic liver disease awaiting liver
transplant. Imaging results will be compared with explant liver pathology analysis.
It is hypothesized that the combination of 1) state-of-the-art multiphase CT or MRI
equipment, 2) contemporary multiphase contrast-enhanced imaging protocols, and
3) new diagnostic criteria will reduce false positive image diagnoses of liver cancer
and ultimately lead to more informed treatment decisions and appropriate organ
allocation and associated priority transplantation in the United States. This trial
examines the new diagnostic criteria, a liver imaging policy draft, developed by the
Organ Procurement and Transplantation Network (OPTN). Pre-qualification of CT and
MRI scanners and images is required at sites wishing to participate. Participating sites
will be transplant centers in the 11 OPTN transplant regions across the United States.
Approximately 25 to 30 centers will participate.

Main Objectives: The main objective of the ACRIN 6690 trial is to compare the
accuracy of radiologic staging of HCC by CT and MRI with the reference standard
provided by explant pathology workup/staging of participants who undergo liver
transplantation for treatment of HCC. Primary analysis will compare CT to MRI
results at the lesion level using core laboratory interpretations of the imaging
studies; secondary analysis will be performed at the patient level.

Participants: Patients diagnosed with HCC and listed or intended for listing for liver
transplant surgery with priority MELD (Model for End-Stage Liver Disease) points
based on the cancer diagnosis will participate. Patients may be waiting for a liver
from a deceased donor to become available or be scheduled to undergo a living donor
adult liver transplant. Patients will enroll in the trial after initial listing with HCC-exception
points to the United Network for Organ Sharing (UNOS) waitlist or once site
investigators confirm intent to list and complete the Declaration of Intent to List Source
Document provided above. In the second scenario, no study-related imaging may be
completed after baseline until UNOS waitlisting with priority MELD points is confirmed
with ACRIN.

Study Design Summary: A total of 440 participants will be accrued to the ACRIN 6690
trial. A minimum of 200 of these participants are being asked to join the optional Eovist
sub-trial, introduced with Amendment 2 to the trial protocol. For the main trial, each site
will image (CT or MRI) a participant approximately every 90 days (or earlier) per the
OPTN/UNOS HCC-exception point update requirements for their region. This imaging
to evaluate disease is considered standard of care. This research trial requires that
complementary imaging (CT or MRI, whichever imaging was not done as the standard
of care) be completed at each 90-day interval. After baseline, this imaging needs to be
completed within 7 days of the standard-of-care imaging that was done for that time interval.
It is permissible to perform both imaging tests on the same day, the order of CT prior to MR is
preferred. The goal is to have imaging with both modalities from within 90 days prior to
transplantation available for comparison with explant pathology findings. Should a
participant undergo local ablative therapy, CT and MRI should be completed no less than
28 days and no more than 60 days after each completed ablative therapy scheme. The
optional Eovist sub-trial adds a third imaging study to each time point. Details are provided
beginning with Amendment 2.