NCT01395030

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

Completed Phase 2 Results posted Last updated 26 September 2018

What this trial tests

Phase 2 trial testing Computed Tomography in Adult Hepatocellular Carcinoma in 64 participants. Completed in 31 May 2018.

Timeline

15 August 2011

Primary endpoint
31 May 2017

31 May 2018

Quick facts

Lead sponsor	Queen's Medical Center
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	64
Start date	15 August 2011
Primary completion	31 May 2017
Estimated completion	31 May 2018
Sites	1 location across United States

Drugs / interventions tested

• Computed Tomography
• 18F-fluoromethylcholine — full drug profile →
• Positron Emission Tomography

Conditions studied

• Adult Hepatocellular Carcinoma — all drugs for Adult Hepatocellular Carcinoma →
• Localized Resectable Adult Liver Carcinoma — all drugs for Localized Resectable Adult Liver Carcinoma →

Sponsor

Queen's Medical Center

Who can join

19 and older, any sex, with Adult Hepatocellular Carcinoma or Localized Resectable Adult Liver Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Area Under the Receiver Operating Characteristic Curve. Primary · Up to study completion at an average of 2.5 years

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).

All primary liver cancers (n=50)

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0.87

HCC only (n=41)

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0.80

Fluorine-18 (18F) Fluoromethylcholine (FCH) PET/CT Parameters for Assessing Hepatocellular Carcinoma (HCC): Sensitivity/Specificity Primary · Up to study completion at an average of 2.5 years

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.

Sensitivity for HCC sub-class S3

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	100

Specificity for HCC sub-class S3

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	73

Statistical Significance of Molecular Pathways Associated With Choline Metabolism as Identified Through Gene Set Enrichment Analysis of Hepatocellular Carcinoma (HCC) Tumor Samples. Primary · Up to study completion at an average of 2.5 years

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 s

HALLMARK_OXIDATIVE_PHOSPHORYLATION

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0.009

HALLMARK_ADIPOGENESIS

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0.012

HALLMARK_PEROXISOME

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0.012

HALLMARK_XENOBIOTIC_METABOLISM

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0.014

HALLMARK_FATTY_ACID_METABOLISM

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0.015

HALLMARK_BILE_ACID_METABOLISM

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0.016

Clinical Liver Disease Severity Based on Liver Fibrosis (Metavir) Stage Primary · Up to 1 year

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.

Fibrosis stage >= F1

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	3.03	1.59 – 5.88

Fibrosis stage >= F2

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	5.29	1.79 – 7.69

Fibrosis stage >= F3

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	5.56	1.85 – 16.7

Fibrosis stage F4

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	6.67	1.33 – 33.3

Number of Participants Comprising Two Distinct PET/CT Imaging Phenotypes (High FCH Uptake vs. Low FCH Uptake) Between the Different Tumor Sub-classes Primary · Up to study completion at an average of 2.5 years

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.

HCC sub-class S1

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	7
18F-fluoromethylcholine PET/CT	6

HCC sub-class S2

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0
18F-fluoromethylcholine PET/CT	4

HCC sub-class S3

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	24
18F-fluoromethylcholine PET/CT	0

Intrahepatic cholangiocarcinoma

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0
18F-fluoromethylcholine PET/CT	8

Primary sarcoma

Group	Value	95% CI
18F-fluoromethylcholine PET/CT	0
18F-fluoromethylcholine PET/CT	1

Adverse events — posted to ClinicalTrials.gov

Time frame: 30 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

18F-fluoromethylcholine PET/CT

Serious: 2/64 (3%)

Deaths: 2/64

Serious adverse events (1 terms)

Reaction	System	18F-fluoromethylcholine PE…
death within 30 days	Surgical and medical procedures	—

Most-reported serious reactions: death within 30 days.

Data from ClinicalTrials.gov NCT01395030 adverse events section.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Underrepresentation of Hispanics in clinical trials for liver cancer in the United States over the past 20 years.
   Monge C, Greten TF. · · 2024 · cited 20× · PMID 38124450 · DOI 10.1002/cam4.6814
2. Transcriptomics Associates Molecular Features with ¹⁸F-Fluorocholine PET/CT Imaging Phenotype and Its Potential Relationship to Survival in Hepatocellular Carcinoma.
   Kwee SA, Tiirikainen M, Sato MM, Acoba JD, et al · · 2019 · cited 11× · PMID 30760520 · DOI 10.1158/0008-5472.can-18-3837
3. PET/CT with ¹⁸F Fluorocholine as an Imaging Biomarker for Chronic Liver Disease: A Preliminary Radiopathologic Correspondence Study in Patients with Liver Cancer.
   Kwee SA, Wong L, Chan OTM, Kalathil S, et al · · 2018 · cited 10× · PMID 29315063 · DOI 10.1148/radiol.2018171333
4. Metabolic characteristics distinguishing intrahepatic cholangiocarcinoma: a negative pilot study of (18)F-fluorocholine PET/CT clarified by transcriptomic analysis.
   Kwee SA, Okimoto GS, Chan OT, Tiirikainen M, et al · · 2016 · cited 4× · PMID 27069767