Fluorine-18 Fluorocholine PET/CT for Liver Cancer

(ExTRACT-HCC Trial)

Overseen By Abrar M Al-Adhmi, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special scan called a fluorine-18 fluorocholine PET/CT to determine if it can predict liver cancer's response to a specific treatment. The focus is on individuals with inoperable liver cancer (specifically, hepatocellular carcinoma) who are about to begin immune checkpoint inhibitor therapy and cannot undergo surgery or other local treatments. Participants must have a liver cancer diagnosis that surgery cannot cure and must already be under an oncologist's care. The trial aims to improve understanding of the scan's ability to foresee a lack of response to the treatment after 16 weeks. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 prior data suggests that fluorine-18 fluorocholine PET/CT is safe for use in liver cancer diagnostics?

Research has shown that fluorine-18 fluorocholine (FCH), used in PET/CT scans, is generally safe and well-tolerated. Its safety profile resembles that of regular choline, a natural nutrient, indicating FCH's suitability for imaging procedures. Studies have not reported any major side effects, making it a reliable choice for detecting liver tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Fluorine-18 fluorocholine PET/CT for liver cancer because it offers a novel way to visualize tumors with potentially greater precision. Unlike standard imaging techniques, such as CT or MRI, which may not clearly differentiate between tumor and normal tissue, this method targets cellular processes specific to cancer cells, enhancing detection accuracy. Additionally, by incorporating genomic liquid biopsies, this approach allows for a more personalized assessment of liver cancer, which can be crucial in tailoring effective treatment plans. This combination of advanced imaging and personalized diagnostics represents a significant step forward in liver cancer management.

What evidence suggests that fluorine-18 fluorocholine PET/CT is effective for predicting treatment response in liver cancer?

Research has shown that a special type of scan, fluorine-18 fluorocholine PET/CT, excels at detecting liver cancer, particularly hepatocellular carcinoma (HCC). One study found that this scan correctly identified cancer in 93% of cases. It is especially effective at detecting certain liver tumors, such as well-differentiated HCC. This method surpasses the more commonly used fluorine-18 fluorodeoxyglucose (FDG) PET/CT scan in finding HCC. In this trial, all participants will undergo diagnostic testing with fluorine-18 fluorocholine PET/CT. These results suggest it might also help predict how well patients respond to certain cancer treatments called immune checkpoint inhibitors. ^{6 7 8 9 10}

Who Is on the Research Team?

Sandi A Kwee, MD

Principal Investigator

The Queen's Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fluorine-18 fluorocholine

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 demonstrated that the [18F]Fluorocholine ([18F]FCH) tracer is effective for detecting primary breast tumors and lung metastases in a murine model, indicating its potential for use in breast cancer imaging.

[18F]FCH/PET may be advantageous for monitoring the response to breast cancer treatments earlier than traditional methods, suggesting it could improve patient management in clinical settings.

NCBI (Pubmed)

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. de Almeida Schirmer, BG., de Araujo, MR., Silveira, MB., et al.[2023]

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]

(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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5407951/

[18F]fluorocholine PET/CT imaging of liver cancer Sensitivity for all tumors based on an abnormal [18F]fluorocholine uptake ratio was 93%, while sensitivity for HCC based on increased tumor [18F]fluorocholine ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02074202

Study Details | To Evaluate the Efficacy and Safety of (18F-FCH) ... This study will provide valuable data on whether these imaging agents can successfully differentiate malignant liver lesions from benign ones. It will also ...

3. withpower.com withpower.com/trial/phase-3-carcinoma-9-2021-191f8

Fluorine-18 Fluorocholine PET/CT for Liver Cancer Trial Overview The study tests if PET/CT scans using fluorine-18 fluorocholine can predict the effectiveness of immune-checkpoint inhibitor therapy in patients ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/51/11/1699

Detection of Hepatocellular Carcinoma with PET/CT: A ... 18 F-fluorocholine was significantly more sensitive than 18 F-FDG at detecting HCC, in particular in well-differentiated forms.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0378603X17302000

Can fluorine-18-fluorodeoxyglucose positron emission ... This study affirms the achievability of 18-F-FDG PET/CT for identification of primary HCC and its extrahepatic metastases.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5875439/

[18F]-choline PET/CT as an imaging biomarker for primary ... In addition, fluorocholine with a known dosimetry has comparable safety profile to that of the native choline (6). Besides the known applications to prostate ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01395030

NCT01395030 | PET/CT in Diagnosing Patients With Liver ... This clinical trial studies positron emission tomography (PET)/computed tomography (CT) in diagnosing patients with liver cancer undergoing surgical resection.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9687226/

PET/CT with 18F-choline or 18F-FDG in Hepatocellular ... In our real-world study, PET/CT with 18 F-FCH or 18 F-FDG influenced clinical management and affected the final outcome for HCC patients treated with 90 Y-TARE.

9. mdpi.com mdpi.com/2075-4418/5/2/189

Chronic Liver Disease and the Detection of Hepatocellular ... Positron emission tomography (PET) using the radiopharmaceutical tracer fluorine-18 fluorocholine (FCh) can elucidate tumors based on ...

10. jnm.snmjournals.org jnm.snmjournals.org/content/47/suppl_1/36P.1

Fluorocholine-(18F) is superior to fluorodeoxyglucose-(18F ... Fluorocholine-(18F) is superior to fluorodeoxyglucose-(18F) for the detection of hepatocellular carcinoma with hybrid positron emission ...