PET/CT in Diagnosing Patients With Liver Cancer Undergoing Surgical Resection

Adult Hepatocellular Carcinoma Clinical Trial

Official title:

Genomic and Imaging Study for Patients Undergoing Surgery for Liver Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01395030
• Other study ID #: RA-2011-025
• Secondary ID: NCI-2012-02095CH
• Status: Completed
• Phase: Phase 2
• Start date: August 15, 2011
• Est. completion date: May 31, 2018

Study information

• Verified date: August 2018
• Source: Queen's Medical Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial studies positron emission tomography (PET)/computed tomography (CT) in diagnosing patients with liver cancer undergoing surgical resection. Diagnostic procedures, such as fluorine-18 fluoromethylcholine PET/CT, may help find and diagnose liver cancer.

Description:

PRIMARY OBJECTIVES:

I. Determine the most optimal fluorine-18 (18F) fluoromethylcholine (FCH) PET/CT parameters for detecting primary hepatocellular carcinoma (HCC) by conducting a clinical radiologic-pathologic correlation study to estimate and compare the receiver operating characteristics of kinetic and static PET measures of tumor FCH metabolism in patients that test positive during screening or conventional imaging.

II. Identify cancer signaling pathways associated with choline metabolism in HCC by profiling the global gene expression patterns in fresh-frozen liver tissue samples that are correlated with the features derived from FCH PET/CT images.

III. Characterize the association between features derived from FCH PET/CT images of the liver and clinical liver disease severity and comparatively evaluate the ability of corresponding gene expression signatures to predictively model HCC disease outcome.

OUTLINE:

Patients undergo 18F-fluoromethylcholine PET/CT within 14 days of surgical resection.

After completion of study treatment, patients are followed up periodically.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: May 31, 2018
• Est. primary completion date: May 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Liver tumor diagnosed histologically as HCC or suspected of being HCC in association with serum alpha-fetoprotein level > 200 or tumor mass with characteristics of malignancy on diagnostic imaging

• Under the care of a surgical attending

• Deemed a surgical candidate and has agreed to surgery to remove a portion of the liver containing tumor

• Child-Pugh A/B

Exclusion Criteria:

• Weight > 350 lbs

• Pregnant or lactating female, a serum pregnancy test will be performed within 2 weeks or less before the date of the FCH PET/CT scan in all women capable of becoming pregnant

• Serious underlying medical condition that would impair patient's ability to tolerate the imaging procedure

• Concurrent treatment with chemotherapy, molecule-selective, biological, or radiotherapeutic agent

Related Conditions & MeSH terms

• Adult Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular
• Liver Neoplasms
• Localized Resectable Adult Liver Carcinoma

Intervention

Diagnostic Test:
• Computed Tomography
Undergo FCH PET/CT

Drug:
• 18F-fluoromethylcholine
Undergo FCH PET/CT

Diagnostic Test:
• Positron Emission Tomography
Undergo FCH PET/CT

Locations

Country	Name	City	State
United States	University of Hawaii Cancer Center	Honolulu	Hawaii

Sponsors (2)

Lead Sponsor	Collaborator
Queen's Medical Centre	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kwee SA, Wong L, Chan OTM, Kalathil S, Tsai N. PET/CT with (18)F Fluorocholine as an Imaging Biomarker for Chronic Liver Disease: A Preliminary Radiopathologic Correspondence Study in Patients with Liver Cancer. Radiology. 2018 Apr;287(1):294-302. doi: 10 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Area Under the Receiver Operating Characteristic Curve.	Area under the receiver operating characteristic curve for detecting resectable hepatocellular carcinoma with prognostically favorable molecular features (Hoshida molecular sub-class S3) based on FCH PET/CT measurement of tumor maximum standardized uptake value (SUVmax).	Up to study completion at an average of 2.5 years
Primary	Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Sensitivity/Specificity	Sensitivity and specificity estimated at a predefined point (ie. Youden's maxima) on the receiver operating characteristic curve for detecting hepatocellular carcinoma with prognostically favorable molecular features (Hoshida molecular sub-class S3) based on FCH PET/CT measurement of tumor maximum standardized uptake value (SUVmax) in patients who underwent subsequent tumor resection.	Up to study completion at an average of 2.5 years
Primary	Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples.	Statistically significant enrichment by sets of genes corresponding to previously-defined molecular pathway signatures was assessed by gene set enrichment analysis (a publicly available algorithm) of whole-genome expression array data obtained from tumors previously characterized by FCH PET/CT. Statistical significance was based on a false discovery rate < 0.05. Tumors demonstrating high choline metabolism (defined by a tumor-liver ratio > 1.0 measured on PET) were assessed for enrichment by publicly-available gene sets. This particular analysis involved the entire Molecular Hallmarks gene signature collection (v6.0) as obtained from the Broad Institute Molecular Signature Database (MSigDB).	Up to study completion at an average of 2.5 years
Primary	Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage	Odds ratios and 95% confidence intervals for histologic liver fibrosis (Metavir) stage >= F1, >= F2, >= F3, and F4 at liver standardized uptake value (SUV) thresholds of 8.3, 8.0, 7.4, and 6.4, respectively. Reference: PMID 29315063.	Up to 1 year
Primary	Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes	HCC tumors were sub-classified using gene expression arrays into 3 distinct prognostically-relevant molecular sub-classes (S1,S2, S3, where S3 is associated with the most favorable clinical prognosis) based on Hoshida et. al (PMID 19723656). The number of tumors comprising two distinct PET/CT imaging phenotypes (high FCH uptake vs. low FCH uptake) was compared between the different sub-classes.	Up to study completion at an average of 2.5 years