18F-Fluciclovine Imaging for Brain Tumors

(CONCORDANT Trial)

Overseen By Antoinette Pimentel

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Baptist Health South Florida

Disqualifiers: Leptomeningeal disease, Prior whole-brain radiation, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is for patients who have had surgery to remove brain metastasis and are planned to have stereotactic radiosurgery (SRS) after their brain surgery. It will be optional for patients to have a pre-surgery 18F-Fluciclovine PET/CT scan. The goal of the study is to determine whether a specific imaging agent, known as 18F-Fluciclovine, will help physicians evaluate the extent of surgery and determine if there is any visible tumor above what MRI alone can identify as well as improve the physicians' ability to detect recurring disease. This agent (18F-Fluciclovine) is investigational for the imaging of brain metastases.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more information.

What data supports the idea that 18F-Fluciclovine Imaging for Brain Tumors is an effective treatment?

The available research shows that 18F-Fluciclovine is effective in detecting brain tumors, especially in cases where other imaging methods like MRI have limitations. It has been shown to identify tumor regions that conventional MRI scans might miss. Studies also indicate that 18F-Fluciclovine is useful in assessing recurrent brain tumors and provides better regional assessment of tumor activity compared to some other imaging techniques. This suggests that 18F-Fluciclovine can be a valuable tool in managing brain tumors by offering more detailed information about the tumor's presence and activity. ^{1 2 3 4 5}

What safety data is available for 18F-Fluciclovine in brain tumor imaging?

Safety data for 18F-Fluciclovine in brain tumor imaging is available from a Phase IIa study and a multicenter Phase IIb trial. These studies evaluated the safety of 18F-Fluciclovine (anti-[18F]FACBC) in patients with malignant glioma and clinically suspected gliomas, respectively. ^{1 6 7 8 9}

Is the drug 18F-Fluciclovine a promising treatment for brain tumors?

Yes, 18F-Fluciclovine is a promising drug for brain tumors. It helps doctors see brain tumors more clearly than some other methods, making it easier to diagnose and plan treatment. It has shown good results in detecting brain tumors that other scans might miss. ^{1 2 10 11 12}

Research Team

Rupesh R Kotecha, MD

Principal Investigator

Miami Cancer Institute/Baptist Health South Florida

Eligibility Criteria

This trial is for adults over 18 who've had brain surgery to remove metastasis and are set for follow-up radiosurgery. They must be in a stable enough condition (ECOG 0-3) and agree to use two effective contraception methods if of reproductive potential. It's not for those with prior whole-brain radiation, MRI contraindications, pregnancy during the study period, breastfeeding without pausing it post-imaging, previous severe reaction to 18F-Fluciclovine or leptomeningeal disease.

Inclusion Criteria

I have been diagnosed with brain metastasis through imaging tests.

I am scheduled for radiation therapy after surgery.

I can care for myself but may not be able to do heavy physical work.

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

Prior anaphylactic reaction to 18F-Fluciclovine

I have had whole-brain radiation therapy before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgery Imaging

Optional pre-surgery 18F-Fluciclovine PET/CT scan to evaluate the extent of surgery

1 day

1 visit (in-person)

SRS Treatment Planning

18F-Fluciclovine PET/CT scan in addition to planning MRI at the time of SRS treatment

Approximately 2-4 weeks after resection

1 visit (in-person)

Follow-up

Participants undergo routine follow-up with 18F-Fluciclovine PET/CT and MRI to monitor resection beds for tumor control and detect patterns of failure

12 months

Multiple visits (in-person)

Treatment Details

Interventions

• 18F-Fluciclovine

Trial Overview The trial tests an imaging agent called 18F-Fluciclovine in patients after brain metastasis surgery but before stereotactic radiosurgery. The aim is to see if this agent can better reveal remaining tumor tissue compared to standard MRI and help detect recurrence more effectively.

Participant Groups

Group I: PET/CT, MRI Experimental Treatment 1 Intervention

All patients will obtain an 18F-Fluciclovine PET/CT scan in addition to the planning MRI at the time of SRS treatment (approximately 2-4 weeks after resection). The value of 18F-Fluciclovine in addition to structural information from the MRI will be analyzed. Patients will continue to undergo 18F-Fluciclovine in addition to MRI during routine follow-up to determine the ability of 18F-Fluciclovine PET/CT to identify areas at risk for marginal failure, monitor resection beds for tumor control, identify patients at risk for disease recurrence, and detect patterns of failure.

Who Is Running the Clinical Trial?

Baptist Health South Florida

Lead Sponsor

Trials

54

Recruited

8,100+

Blue Earth Diagnostics

Industry Sponsor

Trials

43

Recruited

3,100+

Findings from Research

In a phase IIa study involving 5 patients with malignant glioma, anti-[18F]FACBC demonstrated the ability to identify tumor regions that were not visible on conventional CE-T1W MRI, suggesting it may provide a more comprehensive assessment of glioma spread.

The safety profile of anti-[18F]FACBC was favorable, with only mild adverse events reported, indicating that it is a safe diagnostic tool for patients undergoing treatment for malignant glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIa clinical study of [18F]fluciclovine: efficacy and safety of a new PET tracer for brain tumors. Kondo, A., Ishii, H., Aoki, S., et al.[2017]

In a study involving 13 rats with implanted glioblastoma cells, [18F]fluciclovine PET showed similar sensitivity for detecting tumor burden compared to conventional MRI, with median sensitivities of 0.67 for PET and 0.61 for MRI.

Combining [18F]fluciclovine PET with MRI significantly improved detection sensitivity to 0.86, which was 41% higher than MRI alone, indicating that using both imaging techniques together may enhance the assessment of brain tumor burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI and amino acid PET detection of whole-brain tumor burden. Chen, P., Scarpelli, ML., Healey, DR., et al.[2023]

In a study of 27 patients with recurrent gliomas, 18F-Fluciclovine PET imaging was positive for all patients, while contrast-enhanced MRI was indeterminate for three, highlighting 18F-Fluciclovine's potential as a reliable imaging tool when MRI results are unclear.

18F-Fluciclovine provided significantly higher image contrast compared to 11C-Methionine due to its lower background uptake in normal brain tissue, making it a promising option for better tumor visualization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors. Michaud, L., Beattie, BJ., Akhurst, T., et al.[2023]

In a study involving 31 rats with human glioblastoma cell lines, fluciclovine PET imaging showed increased uptake associated with higher levels of the amino acid transporter ASCT2, indicating its potential for assessing brain tumor metabolism.

Fluciclovine PET was effective in visualizing both enhancing and non-enhancing tumors, with greater uptake observed in larger tumors and those with gadolinium enhancement, suggesting these factors should be considered when interpreting PET results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission Tomography. Scarpelli, ML., Healey, DR., Mehta, S., et al.[2022]

F-fluciclovine PET/CT shows high uptake in patients with suspected recurrent high-grade glioma (HGG), effectively identifying tumors with a median lesion-to-background ratio of 21.6, which is significantly higher than other amino acid PET tracers.

In this study of 21 patients, F-fluciclovine PET/CT successfully detected small satellite tumors not visible on MRI in 4 cases, highlighting its potential for improved tumor detection, although its ability to differentiate between tumor recurrence and treatment-related changes remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-Fluciclovine PET/CT in Suspected Residual or Recurrent High-Grade Glioma. Bogsrud, TV., Londalen, A., Brandal, P., et al.[2020]

The PET tracer 18F-fluciclovine (Axumin) has been approved for use in men suspected of having recurrent prostate cancer after previous treatment, indicating its potential role in improving diagnosis.

Studies utilizing systematic sector-based histopathology as a reference standard have been conducted to evaluate the diagnostic accuracy of 18F-fluciclovine PET, highlighting its importance in clinical settings for prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-Fluciclovine PET for Assessment of Prostate Cancer with Histopathology as Reference Standard: A Systematic Review. Seierstad, T., Hole, KH., Tulipan, AJ., et al.[2021]

18F-fluciclovine PET/CT is effective for detecting biochemically recurrent prostate cancer, but it can also reveal incidental findings, such as a pancreatic head mass.

In this case, the pancreatic mass appeared as a photopenic defect on the PET/CT scan and was later confirmed to be a benign serous cystadenoma through MRI, highlighting the importance of further investigation for unexpected findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidental Serous Cystadenoma Presenting as a Photopenic Pancreatic Defect on 18F-Fluciclovine PET/CT. Waltz, J., Mercer, MK., Dani, G., et al.[2023]

The FDA recently approved F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC, F-fluciclovine) PET/CT scans for detecting suspected prostate cancer recurrence in men with elevated PSA levels after treatment.

In a unique case study of a 77-year-old man, the scan revealed not only suspected recurrent prostate cancer but also advanced-stage breast cancer, highlighting the potential for incidental findings during prostate imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic Male Breast Cancer With Increased Uptake on 18F-Fluciclovine PET/CT Scan. Gill, HS., Tade, F., Greenwald, DT., et al.[2018]

The novel tracer 18F-fluciclovine (anti-[18F]FACBC) demonstrated a 100% positive predictive value for detecting gliomas in areas not visible on standard contrast-enhanced MRI, indicating its high diagnostic accuracy.

The tracer was well tolerated among patients, with only 17.5% experiencing mild adverse events, none of which were serious, suggesting it is a safe option for glioma imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Performance and Safety of Positron Emission Tomography Using 18F-Fluciclovine in Patients with Clinically Suspected High- or Low-grade Gliomas: A Multicenter Phase IIb Trial. Wakabayashi, T., Iuchi, T., Tsuyuguchi, N., et al.[2023]

FACBC-PET imaging demonstrated higher contrast in detecting gliomas compared to L-methyl-11C-methionine (MET)-PET, suggesting it may be more effective for glioma diagnosis.

In a study involving six patients suspected of having gliomas, FACBC showed higher lesion-to-normal brain tissue ratios than MET, indicating better assessment capabilities for glioma detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis of Brain Tumors Using Amino Acid Transport PET Imaging with 18F-fluciclovine: A Comparative Study with L-methyl-11C-methionine PET Imaging. Tsuyuguchi, N., Terakawa, Y., Uda, T., et al.[2020]

In a study involving 45 patients with suspected glioma, 18F-fluciclovine PET/CT demonstrated a high positive predictive value of 88.0% for identifying tumor areas that were not visible on traditional imaging, aiding in surgical planning.

The use of 18F-fluciclovine PET/CT led to modifications in the planned extent of tumor resection in nearly half of the cases, indicating its potential to improve surgical outcomes for glioma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining the extent of tumor resection at surgical planning with 18F-fluciclovine PET/CT in patients with suspected glioma: multicenter phase III trials. Wakabayashi, T., Hirose, Y., Miyake, K., et al.[2022]

The study involved 27 women with newly diagnosed locally advanced invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), and found that (18)F-fluciclovine PET/CT effectively visualized all cases of breast cancer, including detecting previously unsuspected extraaxillary nodal metastases in some patients.

While (18)F-fluciclovine showed strong concordance in measuring metabolic tumor volume compared to (18)F-FDG, the weak concordance for SUVmax indicates that these two imaging agents may reflect different biological processes in tumors, suggesting that (18)F-fluciclovine could provide unique insights into breast cancer biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Results of a Prospective Clinical Trial of 18F-Fluciclovine PET/CT in Newly Diagnosed Invasive Ductal and Invasive Lobular Breast Cancers. Ulaner, GA., Goldman, DA., Gönen, M., et al.[2017]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Phase IIa clinical study of [18F]fluciclovine: efficacy and safety of a new PET tracer for brain tumors. [2017]

2. Switzerland pubmed.ncbi.nlm.nih.gov

MRI and amino acid PET detection of whole-brain tumor burden. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission Tomography. [2022]

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

18F-Fluciclovine PET/CT in Suspected Residual or Recurrent High-Grade Glioma. [2020]

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

18F-Fluciclovine PET for Assessment of Prostate Cancer with Histopathology as Reference Standard: A Systematic Review. [2021]

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

Incidental Serous Cystadenoma Presenting as a Photopenic Pancreatic Defect on 18F-Fluciclovine PET/CT. [2023]

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

Metastatic Male Breast Cancer With Increased Uptake on 18F-Fluciclovine PET/CT Scan. [2018]

9. Iran pubmed.ncbi.nlm.nih.gov

Diagnostic Performance and Safety of Positron Emission Tomography Using 18F-Fluciclovine in Patients with Clinically Suspected High- or Low-grade Gliomas: A Multicenter Phase IIb Trial. [2023]

10. Iran pubmed.ncbi.nlm.nih.gov

Diagnosis of Brain Tumors Using Amino Acid Transport PET Imaging with 18F-fluciclovine: A Comparative Study with L-methyl-11C-methionine PET Imaging. [2020]

11. Japan pubmed.ncbi.nlm.nih.gov

Determining the extent of tumor resection at surgical planning with 18F-fluciclovine PET/CT in patients with suspected glioma: multicenter phase III trials. [2022]

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

Initial Results of a Prospective Clinical Trial of 18F-Fluciclovine PET/CT in Newly Diagnosed Invasive Ductal and Invasive Lobular Breast Cancers. [2017]