NCT06732388

Itraconazole in Combination With Ablation for the Prevention of Esophageal Cancer in Patients With High-risk Barrett's Esophagus

Repurposing Itraconazole for Secondary Prevention of Metaplasia and Primary Prevention of Cancer in Patients With High-Risk Barrett's Esophagus in Combination With Ablation

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 64 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well itraconazole works in combination with the usual standard of care endoscopy with ablation for the prevention of esophageal cancer in patients who have high-risk Barrett's esophagus (BE). BE is a condition in which the lining of the esophagus changes and becomes more like the tissue that lines the intestine. People with Barrett's esophagus have a higher risk of developing esophageal cancer. Itraconazole is a drug used to prevent or treat fungal infections. Ablation refers to the removal of abnormal tissue using heat. Endoscopy is a procedure for looking at the esophagus using a long, flexible tube called an endoscope, which has a video camera at the end. Radiofrequency ablation is a type of heat therapy that uses radiofrequency energy (similar to microwave heat) to destroy the abnormal tissue in the esophagus. Giving itraconazole in combination with standard of care endoscopy with ablation may improve the effects of ablation and prevent esophageal cancer in patients with high-risk Barrett's esophagus.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate if itraconazole in the peri-ablation period in participants with high-risk Barrett's esophagus (BE) can accelerate BE regression i.e., achieve complete resolution of intestinal metaplasia (CRIM) faster than the control group. SECONDARY OBJECTIVES: I. To measure the time to event of complete eradication of dysplasia (CED). II. To measure the rate of BE recurrence during routine follow-up. III. To determine the safety and tolerability of itraconazole in participants with high-risk BE. IV. To correlate levels of itraconazole and its primary metabolite hydroxyitraconazole in plasma and esophageal tissues with treatment response. V. To compare biosocial impact on the participants in the itraconazole and control arms. EXPLANATORY OBJECTIVE: I. To correlate the degree of inhibition of Hedgehog (Hh), PI3K-AKT, and VEGFR2 signaling pathways with treatment response. EXPLORATORY OBJECTIVES: I. To determine whether expression (baseline and magnitude of change) of stem cell markers such as LGR5/CD44/DCAMKL1 can predict treatment response. II. To bank blood samples and tissue biopsies for future analyses to understand the determinants of response. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive itraconazole orally (PO) twice daily (BID) on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles as long as there is an absence of disease progression or unacceptable toxicity. Patients undergo usual standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. GROUP II: Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles as long as there is an absence of disease progression or unacceptable toxicity. Patients undergo usual standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. After completion of study treatment, patients are followed up at 12 months.

Conditions

• Barrett Esophagus
• Clinical Stage I Esophageal Adenocarcinoma AJCC v8
• Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8
• Esophageal Adenocarcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tissue biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Endoscopic Procedure	Undergo endoscopy
DRUG	Itraconazole	Given PO
DRUG	Placebo Administration	Given PO
OTHER	Questionnaire Administration	Ancillary studies
PROCEDURE	Radiofrequency Ablation	Undergo radiofrequency ablation

Timeline

• Start date: 2026-10-06
• Primary completion: 2030-02-01
• Completion: 2030-02-01
• First posted: 2024-12-13
• Last updated: 2026-04-13

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study