Clinical trial NCT03694600: Clinical Trial Multi-analyte Blood Test
Official title: Prospective Clinical Trial to Detect Liver Cancer Through Quantification of cfDNA Methylation in Blood Samples: A LAM Insight Trial Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Liver Cirrhosis
Lead sponsor: Helio Genomics
Sponsor class: INDUSTRY
First posted: 2018-10-03
Enrollment: 1900
Sex: ALL
Minimum age (years): 21
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The maximum study duration for any given subject participating in the trial will be approximately 21 months (includes Initial Surveillance Visit and Follow-Up Visits at 6 months, 12 months and 18 months). No study-related lab assessments, imaging or procedures shall be required for any subject after the Study Duration Period.

Subject Eligibility Screening Period: 14 days Study Duration Period: Up to 21 months (includes Initial Surveillance Visit for all subjects and up to three Follow-Up Visits ONLY for subjects with indeterminant findings by diagnostic imaging) The maximum observational window for any subject enrolled in the study is expected to be approximately 21 months (for subjects with indeterminant findings by diagnostic imaging).

Brief summary: This is a clinical trial designed to evaluate the performance of a multi-analyte blood test alone to ultrasound alone for the detection of HCC within a population that is at high risk for HCC due to liver cirrhosis.

Detailed description: This multi-site, prospective study is designed to compare the sensitivity and specificity of a multi-analyte blood test alone to ultrasound alone for the detection of HCC within a population at high risk of HCC due to liver cirrhosis. Subjects will be enrolled until the pre-determined number of subjects are enrolled.

Subjects at high risk for developing HCC due to liver cirrhosis and who are eligible for liver cancer surveillance as determined by the patient's physician and who meet all inclusion and exclusion eligibility criteria as described in this protocol, will be invited to participate in this study. Subjects will then read, understand and sign the Informed Consent Form and the HIPAA Authorization Agreement for Medical Records Form.

For each subject upon enrollment, the following blood analytes will also be determined: creatinine, prothrombin time, bilirubin, blood platelet count, ALT, AST and ALP. The results of all clinical laboratory tests will be recorded by use of the subject's Case Report Form. Whole blood samples drawn for the multi-analyte blood test will be collected (according to the instructions provided with each sample collection kit) by using the multi-analyte Sample Collection, Stabilization and Shipping Kit, and shipped to a central LAM laboratory for testing. Samples will be assayed by laboratory technicians blinded to the results of any other testing. Within the same clinical visit as the blood draws (when possible), subjects will undergo conventional ultrasound to examine the liver. Every subject will then go on to diagnostic imaging by multiphasic MRI. The results of diagnostic imaging will primarily be scored by LI-RADS score and the number and size of any malignant lesions identified will be recorded. The images of all MRI, CT, or ultrasound will be saved and uploaded for evaluation by a blinded, centralized team of radiologists to confirm diagnosis. Any biopsy results or surgical pathology results that are generated for study subjects as part of current clinical practice will also be recorded.

Study procedures will consist of conventional ultrasound to examine the liver, providing blood samples for testing with the multi-analyte blood test and other conventional blood analytes, and diagnostic imaging by multiphasic MRI.

Upon enrolling in the study, subjects will commence the Initial Surveillance Visit (t=0 months). During the Initial Surveillance Visit, all enrolled subjects will undergo ultrasound to examine the liver and provide blood samples for the multi-analyte blood test and for determining conventional blood analytes. Every subject will then go on to diagnostic imaging by multiphasic MRI. The results of diagnostic imaging will primarily be scored by a Liver Reporting and Data System (LI-RADS) score. The data of all diagnostic imaging by MRI will be saved and uploaded for evaluation by a blinded, centralized team of radiologists, which will be used as the basis of the clinical truth for all subjects.

After the Initial Surveillance Visit (t=0 months), subjects with an indeterminant HCC finding by MRI (LI-RADS 3) will be recommended to up to three Follow-Up Visits (t=6 months, t=12 months, and t=18 months) to attempt to resolve the clinical truth for these subjects. Each Follow-Up Visit will consist of an ultrasound to examine the liver, providing blood samples for the multi-analyte blood test , as well as diagnostic imaging by multiphasic MRI.

Although not required by this clinical protocol, any biopsy or surgical pathology results, or any additional imaging (such as multiphasic CT) that are generated for study subjects as part of current clinical practice will also be recorded for each subject and the results shall be made available to the Sponsor if performed within 6 months of a scheduled Visit. Biopsy and surgical pathology results that indicate a malignancy will be used in place of diagnostic imaging as the clinical truth for each subject if performed within 6 months of a scheduled visit and prior to database lock.

All study-related procedures will occur during the Study Duration Period, which consists of the Initial Surveillance Visit for all subjects and up to three Follow-Up Visits for subjects with an initial indeterminant HCC finding (LI-RADS 3) by diagnostic imaging. After this Study Duration Period, no study related blood draws, imaging or procedures will occur for these subjects.

Eligibility criteria: Inclusion Criteria:

* Subject is age 21 to 84 (inclusive)
* Subject is able to read, comprehend and sign the Informed Consent Document
* Subject is willing and able to undergo liver cancer surveillance by ultrasound and the multi-analyte blood Test
* Subject is able and willing to undergo diagnostic imaging by multiphasic MRI with contrast according to the Study Protocol
* Subject has been diagnosed with liver cirrhosis by one or more of the following methods:

  1. Clinical diagnosis by blood analytes (APRI ≥ 1.5 or Bonacini cirrhosis discriminant score ≥ 8 or Lok index \> 0.5)
  2. Ultrasound and Elastography \> 12.5 kPa (Vibration-controlled transient elastography, Point shear wave elastography, Two-dimensional shear wave ultrasound and transient elastography or Magnetic Resonance Elastography)
  3. Diagnostic imaging by CT or MRI (liver cirrhosis indicated on radiology report)
  4. Liver biopsy (liver cirrhosis indicated on pathology report)

Exclusion Criteria:

* The study investigator deems the subject's participation to be unsafe due to an underlying medical condition
* Subject has previously been diagnosed with a primary liver cancer or a non-liver cancer that has metastasized
* Subject has previously submitted a blood sample to Helio Health (HELIO) through a separate clinical protocol
* Subject is unable or unwilling to submit blood samples for testing, undergo ultrasound or undergo diagnostic imaging by multiphasic MRI with contrast as required for the Study Protocol
* Subject has any internal metallic device or fragment, including but not limited to: A pacemaker, artificial joint or valve, surgical clips, pins, plates, screws, wire mesh or shrapnel
* It is unsafe for the subject to receive an MRI contrast dye due to pregnancy or severe kidney disease
* Subject would not routinely be recommended for HCC surveillance
* Subject received an abdominal ultrasound or diagnostic imaging by MRI or CT to image the liver within the past 5 months

Primary outcomes:
measure: Independent performance measure of sensitivity and specificity of a multi-analyte blood test vs ultrasound
timeFrame: 1 month
Secondary outcomes:
measure: Independent performance measure of sensitivity and specificity of a multi-analyte blood test vs ultrasound for the detection of liver cancer lesions that are ≤ 4 cm in diameter.
timeFrame: 1 month
Other outcomes:
Locations:
city: Chandler
country: United States
facility: AZ Liver Health (Chandler)
state: Arizona
city: Peoria
country: United States
facility: AZ Liver Health (Glendale, Peoria)
state: Arizona
city: Tucson
country: United States
facility: AZ Liver Health (Tucson)
state: Arizona
city: Tucson
country: United States
facility: Banner University Hospital (University of Arizona Tucson)
state: Arizona
city: Irvine
country: United States
facility: Alliance Research Centers
state: California
city: Los Angeles
country: United States
facility: University of South California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: Fort Myers
country: United States
facility: Covenant Metabolic LLC
state: Florida
city: Gainesville
country: United States
facility: University of Florida Clinical and Translational Science Institute
state: Florida
city: Miami
country: United States
facility: University of Miami - Schiff Center for Liver Diseases
state: Florida
city: Naples
country: United States
facility: Gastroenterology Group of Naples
state: Florida
city: Sarasota
country: United States
facility: Covenant Metabolics LLC
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Research Institute
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: St Luke's Hospital of Kansas City
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Kansas City
country: United States
facility: Kansas City Research Institute (KCRI)
state: Missouri
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine
state: Ohio
city: Memphis
country: United States
facility: Gastro One in Memphis
state: Tennessee
city: Nashville
country: United States
facility: Quality Medical
state: Tennessee
city: Dallas
country: United States
facility: Liver Center of Texas
state: Texas
city: Dallas
country: United States
facility: Methodist Dallas Medical Center
state: Texas
city: Edinburg
country: United States
facility: SouthTexas Research Institute
state: Texas
city: El Paso
country: United States
facility: Texas Gastro Clinic
state: Texas
city: Houston
country: United States
facility: Konkord Research
state: Texas
city: San Antonio
country: United States
facility: Texas Liver Institute - American Research Corp.
state: Texas
city: Waco
country: United States
facility: Impact Research Institute
state: Texas
city: Norfolk
country: United States
facility: Digestive & Liver Disease Specialists (DLDS) - Norfolk
state: Virginia
city: Richmond
country: United States
facility: VA Richmond
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center (University of Washington)
state: Washington
city: Seattle
country: United States
facility: Liver Institute Northwest
state: Washington
Study officials:
affiliation: Helio Genomics
name: Taggart, PhD
role: STUDY_DIRECTOR
References: