Fluorine-18 Fluorocholine PET/CT for Liver Cancer

(ExTRACT-HCC Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Sandi A Kwee, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Queen's Medical Centre

Must be taking: Immune checkpoint inhibitors

Must not be taking: Non-targeted therapeutics

Disqualifiers: Pregnancy, Serious medical condition, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This prospective clinical trial will evaluate PET/CT and genomic liquid biopsy based biomarkers as predictors of clinical therapeutic response to immune-checkpoint inhibitor (ICI) therapy for patients with inoperable hepatocellular carcinoma (HCC). The primary objective of this diagnostic trial is to assess the accuracy of pre-treatment fluorine-18 (18F-) fluorocholine (FCH) PET/CT for predicting a lack of objective response (LOR) after 16 weeks of ICI therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on a non-targeted therapeutic agent while participating in the trial.

What data supports the effectiveness of the treatment Fluorine-18 fluorocholine for liver cancer?

Research shows that Fluorine-18 fluorocholine PET/CT is useful in predicting outcomes and treatment responses in liver cancer, specifically hepatocellular carcinoma. It has been effective in detecting liver tumors and monitoring treatment responses, which suggests its potential usefulness in managing liver cancer. ^{1 2 3 4 5}

Is 18F-Fluorocholine PET/CT safe for use in humans?

Preclinical studies in mice have been conducted to assess the safety of 18F-Fluorocholine, including its toxicity and how it spreads in the body. These studies are important steps before human trials, suggesting that it has been considered safe enough to proceed to further testing in humans. ^{1 2 3 6 7}

How does 18F-Fluorocholine PET/CT differ from other treatments for liver cancer?

18F-Fluorocholine PET/CT is unique because it uses a special imaging tracer to detect liver cancer by targeting altered choline metabolism, which is more effective than traditional FDG PET/CT for certain liver tumors. This imaging technique helps in diagnosing and predicting treatment outcomes for hepatocellular carcinoma, offering a more sensitive approach to detecting and monitoring liver cancer. ^{1 2 3 8 9}

Research Team

Sandi A Kwee, MD

Principal Investigator

The Queen's Medical Center

Eligibility Criteria

This trial is for adults with inoperable liver cancer (Hepatocellular Carcinoma) who are under a medical oncologist's care, have certain levels of liver function and no serious conditions that would affect their ability to undergo imaging. Pregnant or lactating women and those on non-targeted cancer therapies cannot participate.

Inclusion Criteria

ALT and AST ≤5x upper limit of normal

I have at least one tumor that can be measured on a scan.

My doctor thinks I should get immune therapy due to past treatment failure and my current health status.

Exclusion Criteria

I have a health condition that makes it hard for me to undergo imaging tests.

I am currently not on any non-targeted cancer treatments but can be in an ICI trial.

I am not pregnant or breastfeeding.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Testing

Participants undergo FCH PET/CT and genomic liquid biopsy before ICI treatment. FDG PET/CT may be performed if needed.

1-2 weeks

Treatment

Participants receive immune-checkpoint inhibitor (ICI) therapy for 16 weeks.

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment using RECIST v1.1 criteria.

4 weeks

Treatment Details

Interventions

• Fluorine-18 fluorocholine (Imaging Agent)

Trial Overview The study tests if PET/CT scans using fluorine-18 fluorocholine can predict the effectiveness of immune-checkpoint inhibitor therapy in patients after 16 weeks. It also looks at genomic markers from liquid biopsies as potential predictors.

Participant Groups

Group I: Tested with Biomarkers Experimental Treatment 1 Intervention

For this single arm study, all enrolled subjects will undergo diagnostic testing with FCH PET/CT and genomic liquid biopsy before treatment involving an immune checkpoint inhibitor agent. A fluorine-18 fluorodeoxyglucose (FDG) PET/CT may also be performed before treatment and after 8 weeks if the pre-treatment FCH PET/CT shows low or heterogeneous tumor uptake.

Who Is Running the Clinical Trial?

Queen's Medical Centre

Lead Sponsor

Trials

12

Recruited

1,900+

Queen's Medical Center

Lead Sponsor

Trials

24

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a study of 29 patients with early-stage hepatocellular carcinoma (HCC), 18F-fluorocholine PET/CT imaging effectively predicted prognosis, showing that a baseline SUVmax value below 13 was linked to significantly longer progression-free survival (17.7 months vs. 5.1 months for higher values).

A greater than 45% reduction in SUVmax after treatment indicated a better response, correlating with a mean progression-free survival of 36.1 months compared to 11.6 months for those with less reduction, suggesting that 18F-FCH PET/CT can help identify patients who may need additional therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline and Post-treatment 18F-Fluorocholine PET/CT Predicts Outcomes in Hepatocellular Carcinoma Following Locoregional Therapy. Wallace, MC., Sek, K., Francis, RJ., et al.[2020]

Fluoromethylcholine (FCH) PET imaging effectively visualized recurrent multifocal hepatocellular carcinoma in a patient where traditional F-18 FDG PET showed poor results.

The lesions identified by FCH PET closely matched the findings from CT hepatic angiography, suggesting that FCH may be a more reliable imaging tracer for certain liver tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoromethylcholine PET in recurrent multifocal hepatoma. Lenzo, NP., Anderson, J., Campbell, A., et al.[2016]

In a study of 81 patients with chronic liver disease, (18)F-fluorocholine demonstrated significantly higher sensitivity (88%) for detecting hepatocellular carcinoma (HCC) compared to (18)F-FDG (68%), particularly in well-differentiated HCC cases.

While (18)F-fluorocholine was better at detecting HCC, (18)F-FDG was more effective at identifying other malignancies and showed higher specificity in non-malignant sites, suggesting that using both tracers together may provide the best diagnostic results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of hepatocellular carcinoma with PET/CT: a prospective comparison of 18F-fluorocholine and 18F-FDG in patients with cirrhosis or chronic liver disease. Talbot, JN., Fartoux, L., Balogova, S., et al.[2022]

In a study of 172 prostate cancer patients, a positive (18)F-fluorocholine (FCH) PET/CT scan was found in 137 patients, significantly influencing treatment plans in 43.6% of cases, indicating its value in managing biochemical recurrence.

Quantitative parameters from FCH PET/CT, such as standardized added metabolic activity (SAM) and SUVmean, were identified as independent predictors of progression-free survival, with better scores correlating to longer survival times (up to 49 months) compared to poorer scores (as low as 11 months).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of metabolic parameters and clinical impact of ¹⁸F-fluorocholine PET/CT in biochemical recurrent prostate cancer. Colombié, M., Campion, L., Bailly, C., et al.[2022]

The study evaluated the safety and efficacy of [(18)F]Fluorocholine ([(18)F]FCH) for prostate cancer, which is necessary for its approval as a new radiopharmaceutical in Brazil.

Key assessments included acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry, and microPET imaging, providing essential data to support its use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]fluorocholine in mice. Silveira, MB., Ferreira, SM., Nascimento, LT., et al.[2018]

The study of 18F-Fluorocholine (FCH) shows that it has rapid pharmacokinetics in both mice and humans, with biodistribution stabilizing after just 10 minutes, making it a promising oncologic probe for PET imaging.

The kidneys are identified as the dose-critical organ for 18F-FCH, which limits the safe administration level to 4.07 MBq/kg (0.110 mCi/kg) in human studies, ensuring patient safety during imaging procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and radiation dosimetry of 18F-fluorocholine. DeGrado, TR., Reiman, RE., Price, DT., et al.[2022]

(18)F-fluorocholine PET/CT imaging shows significantly lower uptake in intrahepatic cholangiocarcinoma (ICC) tumors compared to hepatocellular carcinoma (HCC) tumors, suggesting limited effectiveness for detecting ICC.

Gene expression analysis indicates that ICC tumors exhibit a hyper-glycolytic phenotype, with increased expression of glucose transporter 1 (GLUT-1) and down-regulation of lipid metabolism pathways, highlighting distinct metabolic characteristics between ICC and HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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., et al.[2022]

In a study involving 31 patients with hepatocellular carcinoma (HCC) and 4 with intrahepatic cholangiocarcinoma (ICC), [18F]fluorocholine PET/CT demonstrated a high sensitivity of 93% for detecting tumors based on abnormal uptake ratios, and 84% specifically for HCC, indicating its effectiveness in identifying lipogenic tumors.

The analysis revealed that HCC tumors have significantly higher levels of saturated phosphatidylcholines, suggesting they rely on fatty acid metabolism for their growth, although the variability in [18F]fluorocholine uptake indicates that not all HCC tumors exhibit the same metabolic characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]Fluorocholine PET/CT Imaging of Liver Cancer: Radiopathologic Correlation with Tissue Phospholipid Profiling. Kwee, SA., Sato, MM., Kuang, Y., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Baseline and Post-treatment 18F-Fluorocholine PET/CT Predicts Outcomes in Hepatocellular Carcinoma Following Locoregional Therapy. [2020]

2. Australia pubmed.ncbi.nlm.nih.gov

Fluoromethylcholine PET in recurrent multifocal hepatoma. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Comparison of [18F]Fluorocholine and [18F]Fluordesoxyglucose for assessment of progression, lung metastasis detection and therapy response in murine 4T1 breast tumor model. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Detection of hepatocellular carcinoma with PET/CT: a prospective comparison of 18F-fluorocholine and 18F-FDG in patients with cirrhosis or chronic liver disease. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Prognostic value of metabolic parameters and clinical impact of ¹⁸F-fluorocholine PET/CT in biochemical recurrent prostate cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]fluorocholine in mice. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and radiation dosimetry of 18F-fluorocholine. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Metabolic characteristics distinguishing intrahepatic cholangiocarcinoma: a negative pilot study of (18)F-fluorocholine PET/CT clarified by transcriptomic analysis. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

[18F]Fluorocholine PET/CT Imaging of Liver Cancer: Radiopathologic Correlation with Tissue Phospholipid Profiling. [2019]