FAZA PET/MRI Scan for Gastroesophageal Cancer

Overseen By Nirushini Sivasothy

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must be taking: Platinum-based chemotherapy

Disqualifiers: Pregnancy, Breastfeeding, MR contraindication, others

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

Compensation: Varies

Number of Visits: 3

Duration: Varies based on chemotherapy regimen

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm, pilot study of PET/MRI scan with radiotracer 18F-Fluoroazomycin Arabinoside (FAZA) before and after standard of care platinum-based chemotherapy for patients with metastasized Gastro-Oesophageal Cancer. Gastroesophageal cancer (GEC) accounted for 2,3000 deaths in Canada in 2017 and majority of the patients present or develop metastatic disease following diagnosis. These patients are treated with platinum-based chemotherapy. There is currently no biomarker that can be used to predict the therapy responses. Additionally, patients that do not respond to the chemotherapy often deteriorate rapidly and are unable to receive second line therapy. Intratumoral hypoxia (low oxygen concentration) is a signature feature of aggressive and resistant tumour phenotype. Accurately predicting hypoxia in solid tumours offers an innovative and rational pradigm for predicting therapy responses. PET/MRI is an imaging technique combining the Positron Emission Tomography (PET) scan with Magnetic Resonance Imaging (MRI) scan. A radiotracer called 18F-Fluoroazomycin Arabinoside (FAZA) is used as a type of "dye" in the PET/MRI scan. The primary goal of the study is to validate FAZA PET/MRI as a biomarker of hyupoxia in setting of gastro-oesophageal carcinoma. Patients with GEC will undergo FAZA PET/MRI scan before and after the standard of care chemotherapy. This would be correlated with clinical outcome in patients with metastatic GEC that have different responses to chemotherapy. Ultimately, we hope that the use FAZA PET/MRI in the study can help select the most effective treatment method for advanced GEC to extend life and improve quality of life while minimizing toxicity and healthcare costs. The study subjects' clinical management will not be changed based on the PET-MR scan within the trial.

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

The trial information does not specify whether you need to stop taking your current medications. It seems likely that you can continue your current medications, as the study focuses on imaging and does not change your clinical management.

What data supports the effectiveness of the drug 18F-Fluoroazomycin Arabinoside (FAZA) for gastroesophageal cancer?

Research shows that FAZA is effective in identifying low-oxygen areas in tumors, which is important for understanding how well a tumor might respond to treatments like radiation. While this has been studied in other cancers, such as head and neck cancer, it suggests potential usefulness in gastroesophageal cancer as well. ^{1 2 3 4 5}

Is the FAZA PET/MRI scan safe for humans?

The studies on 18F-Fluoroazomycin Arabinoside (FAZA) primarily focus on its use as a PET tracer for identifying low-oxygen areas in tumors, and they do not report any specific safety concerns for humans. However, these studies do not provide detailed safety data, so it's important to discuss potential risks with your healthcare provider. ^{1 2 3 6 7}

How does the FAZA PET/MRI scan treatment for gastroesophageal cancer differ from other treatments?

The FAZA PET/MRI scan is unique because it uses a special tracer, (18)F-fluoroazomycin arabinoside (FAZA), to identify low-oxygen areas within tumors, which can be crucial for understanding tumor behavior and planning treatment. This approach is different from standard treatments as it provides detailed imaging of tumor hypoxia, which is not typically assessed in routine cancer treatments. ^{1 2 3 5 6}

Research Team

Patrick Veit-Haibach, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults over 18 with advanced gastroesophageal cancer who can lie down for at least 30 minutes and have a kidney function test (GFR) above 45 ml/min. It's not suitable for those allergic to contrast agents, pregnant or breastfeeding women, anyone unable to consent, or those with allergies to ethanol.

Inclusion Criteria

Patients with de novo or secondary metastasized gastro-oesophagesal cancer (adenocarcinoma)

Glomerular Filtration rate> 45 ml/min

No allergy to contrast agents

Exclusion Criteria

Contraindication for MR as per current institutional guidelines

Inability to lie supine for at least 30 minutes

Any patient who is pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Imaging

Participants undergo FAZA PET/MRI scan to measure hypoxia before chemotherapy

2 weeks

1 visit (in-person)

Treatment

Participants receive standard of care platinum-based chemotherapy

Varies based on chemotherapy regimen

Post-treatment Imaging

Participants undergo FAZA PET/MRI scan to measure hypoxia after chemotherapy

Immediately after chemotherapy

1 visit (in-person)

Follow-up

Participants are monitored for clinical outcomes and tumor marker ctDNA in blood samples

3 months

1 visit (in-person)

Treatment Details

Interventions

• 18F-Fluoroazomycin Arabinoside (FAZA)

Trial Overview The study tests if a PET/MRI scan using a special dye called FAZA can predict how well patients respond to standard platinum-based chemotherapy. Patients will get scanned before and after treatment to see if the level of oxygen in their tumors correlates with their response.

Participant Groups

Group I: FAZA PET/MRI scan Experimental Treatment 1 Intervention

FAZA PET/MRI scan before and after the standard of care chemotherapy

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

The study identified the reversible two-tissue compartment model with blood volume parameter (2T4k+VB) as the best method for analyzing the kinetics of the PET tracer [(18)F]FAZA in non-small cell lung cancer patients, based on dynamic scans from nine participants.

It was found that using image-derived plasma input functions (IDIF) with venous blood samples can effectively replace traditional arterial blood sampling for analyzing [(18)F]FAZA studies, simplifying the process without compromising accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic analysis of [18F]FAZA in non-small cell lung cancer patients. Verwer, EE., van Velden, FH., Bahce, I., et al.[2021]

The novel azomycin nucleosides beta-2-FAZA and beta-3-FAZL were synthesized and showed similar radiosensitization properties to the existing PET tracer FAZA, with sensitizer enhancement ratios of about 1.8 in HCT-116 cancer cells.

These new compounds have slightly lower partition coefficients than FAZA, which may influence their uptake and effectiveness in imaging tumor hypoxia, potentially improving the diagnosis and treatment of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and hypoxia selective radiosensitization potential of beta-2-FAZA and beta-3-FAZL: fluorinated azomycin beta-nucleosides. Kumar, P., Emami, S., Kresolek, Z., et al.[2019]

In a study involving 10 patients with advanced non-small cell lung cancer, the relationship between tumor blood flow (TBF) and the uptake of the PET tracer (18)F-FAZA was explored, revealing that decreased TBF does not always correlate with lower (18)F-FAZA uptake, indicating a more complex interaction than previously thought.

The findings suggest that areas of high (18)F-FAZA uptake can exist alongside high TBF, challenging the assumption that hypoxia (indicated by (18)F-FAZA uptake) is solely linked to low perfusion, and highlighting the importance of multiparametric analysis in understanding tumor biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiparametric Analysis of the Relationship Between Tumor Hypoxia and Perfusion with ¹⁸F-Fluoroazomycin Arabinoside and ¹⁵O-H₂O PET. Iqbal, R., Kramer, GM., Verwer, EE., et al.[2017]

In a pilot study involving 11 patients with laryngeal squamous cell carcinoma, (18)F-FAZA-PET/CT scans detected hypoxic regions in 9 out of 11 tumors, indicating its potential utility in identifying tumor hypoxia.

However, the study found no clear correlation between (18)F-FAZA uptake and established hypoxia markers, suggesting that further research is needed to validate the accuracy of (18)F-FAZA-PET for guiding radiotherapy planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of hypoxic subvolumes in laryngeal cancer with (18)F-fluoroazomycinarabinoside ((18)F-FAZA)-PET/CT scanning and immunohistochemistry. Bruine de Bruin, L., Bollineni, VR., Wachters, JE., et al.[2019]

In a study involving 9 non-small cell lung cancer patients, both Logan graphic analysis and spectral analysis provided highly accurate quantifications of (18)F-FAZA uptake, correlating well with traditional nonlinear regression methods.

The study found that while tumor-to-blood ratios (SUVr) were comparable, they exhibited significant bias at high volumes of distribution, suggesting that parametric methods may be more reliable for precise hypoxia imaging in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parametric methods for quantification of 18F-FAZA kinetics in non-small cell lung cancer patients. Verwer, EE., Bahce, I., van Velden, FH., et al.[2017]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetic analysis of [18F]FAZA in non-small cell lung cancer patients. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Synthesis and hypoxia selective radiosensitization potential of beta-2-FAZA and beta-3-FAZL: fluorinated azomycin beta-nucleosides. [2019]

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

Multiparametric Analysis of the Relationship Between Tumor Hypoxia and Perfusion with ¹⁸F-Fluoroazomycin Arabinoside and ¹⁵O-H₂O PET. [2017]

4. Germany pubmed.ncbi.nlm.nih.gov

Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: a pilot study. [2018]

5. Japan pubmed.ncbi.nlm.nih.gov

Prognostic value of PET/CT with (18)F-fluoroazomycin arabinoside for patients with head and neck squamous cell carcinomas receiving chemoradiotherapy. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

Assessment of hypoxic subvolumes in laryngeal cancer with (18)F-fluoroazomycinarabinoside ((18)F-FAZA)-PET/CT scanning and immunohistochemistry. [2019]

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

Parametric methods for quantification of 18F-FAZA kinetics in non-small cell lung cancer patients. [2017]