Imaging Biomarker for Esophageal Cancer

Overseen By Steven Lin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, Lactation, Allergic reaction, others

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

Compensation: Varies

Number of Visits: 1

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to detect and understand esophageal cancer using an 18F-FAraG PET scan, which employs the compound ArabinoFuranosylGuanine [18F]F-AraG. Researchers aim to determine if this scan can identify tumors and predict patient response to treatment. Participants will undergo these scans to help gather crucial data. Individuals with locally advanced esophageal cancer who are about to begin combined radiation and systemic therapy may qualify for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the 18F-FAraG PET scan is safe for detecting tumors in esophageal cancer patients?

Research has shown that 18F-FAraG, the imaging tracer used in this trial, primarily identifies and highlights certain cells in the body. Earlier studies demonstrated that this tracer interacts with specific immune cells without causing major issues.

As an early-phase trial, the main focus is on assessing safety and determining the optimal dose. Consequently, there is limited data on its effects in humans. However, early studies suggest that the tracer is generally well-tolerated, with participants typically experiencing no major side effects during the imaging process.

While early results are promising, this trial aims to gather more detailed safety information. Participants will be closely monitored to ensure the tracer's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the 18F-FAraG PET scan because it offers a new way to image esophageal cancer that could improve diagnosis and treatment planning. Unlike standard imaging techniques, such as CT and MRI, which provide structural images, the 18F-FAraG PET scan targets specific cellular activity related to cancer metabolism, potentially revealing how active the cancer is at a metabolic level. This could lead to more personalized treatment plans and help monitor how well a treatment is working, offering a more dynamic view of the disease than current methods.

What evidence suggests that the 18F-FAraG PET scan is effective for detecting esophageal cancer?

Research has shown that 18F-FAraG PET scans, which participants in this trial will undergo, are being studied for their ability to detect tumors in esophageal cancer and predict patient response to treatment. This imaging agent interacts with T-cells, a type of immune cell, to highlight cancer activity in the body. 18F-FAraG is also a type of guanosine analog, a compound effective in treating diseases related to T-cells. Although more studies are needed to confirm its effectiveness specifically for esophageal cancer, these early findings suggest it could be a promising tool for better understanding and managing the disease. ^{1 2 3 6 7}

Who Is on the Research Team?

Steven H. Lin, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with untreated esophageal cancer larger than 2 cm, who will receive chemo and radiation. They must be able to consent, not pregnant or breastfeeding, agree to use birth control, and have a body weight under 400 pounds without conditions preventing imaging.

Inclusion Criteria

Ability to provide written informed consent in accordance with institutional policies

Female participants of childbearing potential must have a negative serum or urine pregnancy test within 1 week of the proposed investigational PET/CT scan(s) prior to injection of the investigational radiopharmaceutical

I have an untreated esophagus cancer larger than 2 cm and will get systemic therapy with radiation.

Exclusion Criteria

Pregnant or lactating females

History of allergic reaction to intravenous contrast

I weigh over 400 pounds or have a condition that prevents me from undergoing certain scans.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Imaging

Participants undergo standard-of-care imaging and 18F-FAraG PET scan before starting treatment

1 week

1 visit (in-person)

Chemoradiation Treatment

Participants receive chemoradiation treatment for esophageal cancer

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ArabinoFuranosylGuanine [18F]F-AraG

Trial Overview The trial is testing if a PET scan using the tracer ArabinoFuranosylGuanine (18F-F-AraG) can detect esophageal tumors and predict how well patients respond to chemoradiation treatment.

How Is the Trial Designed?

Group I: 18F-FAraG PET Experimental Treatment 1 Intervention

Participants found to be eligible to take part in this study, participant will have a 18F-FAraG PET scan as described below. Before you start treatment, you will have standard-of-care imaging and then undergo the research 18F-FAraG PET scan. About 20 minutes before the injection of the 18F-FAraG imaging tracer, you will drink two 8-ounce bottles of water to help clear the imaging tracer from your kidneys.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 24 esophageal cancer patients, a change in tumor volume measured by FDG-PET was the only parameter that effectively identified patients who had a complete response to neoadjuvant therapy after chemoradiation.

Quantitative PET parameters, such as peak and average standardized uptake values, did not differentiate between residual tumors and inflammation caused by treatment, indicating limitations in using these metrics for assessing therapy response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of response to neoadjuvant therapy by quantitative 2-deoxy-2-[18F]fluoro-D-glucose with positron emission tomography in patients with esophageal cancer. Arslan, N., Miller, TR., Dehdashti, F., et al.[2019]

The study found that [18F]fluorodeoxyglucose PET/CT scans performed after the first cycle of chemotherapy did not reliably predict histopathological response in patients with adenocarcinoma of the esophagus, as there was no significant correlation between metabolic changes and tumor viability.

However, in a subgroup of patients who had their PET scans within 16 days of starting chemotherapy, a specific measure called total lesion glycolysis (ΔTLG) showed a significant association with histopathological response, suggesting that ΔTLG could be a potential predictor if assessed early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18 F]Fluorodeoxyglucose PET/CT and prediction of histopathological response to neoadjuvant chemotherapy for adenocarcinoma of the oesophagus and oesophagogastric junction. Harustiak, T., Zemanova, M., Fencl, P., et al.[2018]

In a study of 52 patients with locally advanced esophageal squamous cell carcinoma, the post-treatment SUVmax of the primary tumor was found to be a significant predictor of achieving pathological complete remission (pCR), although its predictive value was considered modest.

Baseline measurements of total lesion glycolysis and SUVmax of nodal metastases were identified as strong independent predictors of overall survival and recurrence-free survival, highlighting their potential importance in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET/CT in the evaluation of treatment response to neoadjuvant chemoradiotherapy and prognostication in patients with locally advanced esophageal squamous cell carcinoma. Yuan, H., Tong, DK., Vardhanabhuti, V., et al.[2019]

In a study of 51 esophageal squamous cell carcinoma (ESCC) patients, higher F-FDG uptake (measured as SUVmax) was significantly correlated with the expression of glucose transporters (GLUT-1 and GLUT-3) and tumor-associated macrophages (CD163), indicating their role in tumor metabolism.

The study found that these molecular markers, along with microvessel density (CD34), are associated with the tumor stage and extent of ESCC, suggesting they may help in understanding the mechanisms behind F-FDG uptake in this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular biological correlation of fluorine-18 fluorodeoxyglucose uptake in esophageal squamous cell carcinoma. Hirose, Y., Kaida, H., Kawahara, A., et al.[2019]

FLT-PET imaging can detect early changes in tumor proliferation in esophageal cancer patients undergoing chemoradiotherapy, showing a significant reduction in tumor uptake of FLT within 24 hours after treatment, which is more pronounced than changes observed with FDG-PET.

The study found a strong correlation between FLT uptake and Ki-67 expression, indicating that FLT-PET is a more specific method for assessing early treatment response compared to FDG-PET, potentially leading to better individualized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H-fluorothymidine using preclinical tumor models. Apisarnthanarax, S., Alauddin, MM., Mourtada, F., et al.[2016]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20838911/

deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine: a novel ... We have synthesized 2'-deoxy-2'-[(18)F]fluoro-9-β-D-arabinofuranosylguanine ([(18)F]F-AraG) and investigated its uptake in T cells.

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06414902?draw=2&rank=1

18F-AraG PET/CT as a Non-Invasive Imaging Biomarker ... To learn if 18F-FAraG PET scans can find tumors in participants with esophageal cancer and predict a participant's response to treatment. Detailed Description.

3. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-0858.html

18F-ARAG PET/CT as a non-invasive imaging biomarker ... Description. To learn if 18F-FAraG PET scans can find tumors in participants with esophageal cancer and predict a participant's response to treatment.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11092840/

Feasibility study: [18F]F-AraG PET for cardiac imaging In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), ...

5. researchgate.net researchgate.net/publication/46256837_Synthesis_of_2'-Deoxy-2'-18FFluoro-9-b-D-Arabinofuranosylguanine_a_Novel_Agent_for_Imaging_T-Cell_Activation_with_PET

Deoxy-2′-[18F]Fluoro-9-β-D-Arabinofuranosylguanine: a ... 9-(β-D-Arabinofuranosyl)guanine (AraG) is a guanosine analog that has a proven efficacy in the treatment of T-cell lymphoblastic disease.

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/484111

18F-AraG PET/CT as a Non-Invasive Imaging Biomarker ... To learn if 18F-FAraG PET scans can find tumors in participants with esophageal cancer and predict a participant's response to treatment.

7. mycancergenome.org mycancergenome.org/content/drugs/[18F]F-AraG/

[18F]F-AraG A radioconjugate composed of the guanosine analog arabinosyl guanine (Ara-G), a high-affinity substrate for both cytoplasmic deoxycytidine kinase (DCK) and ...