Itraconazole to Prevent Recurrent Barrett's Esophagus

Itraconazole Repurposing to Reduce Residual Cancer Risk in Patients With High-risk Barrett's Esophagus After Ablation

Recurrent Barrett's esophagus (BE) that occurs at the rate of 12.4%/year is the Achilles heel of the endoscopic treatment of high-risk BE. Over time, after eradication, BE ultimately recurs in as many as 30-50% of the patients putting them at risk for esophageal adenocarcinoma (EAC), thereby undoing the benefits of an effective initial therapy. Also, recurrences need retreatments that increase costs and complications including strictures and refractory ulcerations. A therapy to prevent recurrent BE does not currently exist. Itraconazole with its ability to inhibit important molecular pathways related to BE development could enhance the long-term effectiveness of endoscopic eradication of high-risk BE, thereby promoting a long-term cure

Study Overview

• Status: Active, not recruiting
• Conditions: Barrett Oesophagitis With Dysplasia
• Intervention / Treatment: Drug: Itraconazole in capsule form; Drug: Itraconazole in solution form

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with Barrett's esophagus with either confirmed low-grade dysplasia or high grade dysplasia or intramucosal/T1 adenocarcinoma (see histologic review) being considered for endoscopic treatment. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

• Inability to provide informed consent, New York Heart Association class III or IV congestive heart failure (CHF), liver function tests (LFT)>3X upper limit of normal, drug allergy to itraconazole, pregnancy, prolonged QTc (>450 ms for men and QTc>470 ms for women) or critical drug interactions with other medications metabolized by cytochrome P450(CYP)3A4.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Itraconazole in capsule form; Participants in this arm will receive the capsule form of itraconazole	Drug: Itraconazole in capsule form; Patients with high-risk BE will receive two weeks of itraconazole in the capsule form (N=5).
Active Comparator: Itraconazole in solution form; Participants in this arm will receive the solution form of itraconazole	Drug: Itraconazole in solution form; Patients with high-risk BE will receive two weeks of itraconazole in the solution form (N=5).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Itraconazole drug and blood levels	The primary endpoint will be the tissue (in esophageal biopsies) and blood concentrations of itraconazole.	8-12 months after study initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of itraconazole	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	8-12 months after study initiation
Effects of itraconazole on Gli1 expression	Reduction in Gli1 expression	8-12 months after study initiation
Effects of itraconazole on (Patched) PTCH expression	Reduction in PTCH expression by IHC	8-12 months after study initiation
Effects of itraconazole on AKT pathway	Reduction in Phospho S6 by IHC	8-12 months after study initiation
Effects of itraconazole on angiogenesis	Reduction in Vascular endothelial growth factor (VEGF)/ Vascular endothelial growth factor receptor type 2 (VEGFR2) by IHC	8-12 months after study initiation

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: University of Texas, Southwestern Medical Center at Dallas

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2022
• Primary Completion (Actual): February 23, 2024
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: November 1, 2022
• First Posted (Actual): November 8, 2022

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Barrett's esophagus
• Additional Relevant MeSH Terms: Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Gastroenteritis; Precancerous Conditions; Esophagitis; Barrett Esophagus; Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP3A Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Hydroxyitraconazole
• Other Study ID Numbers: 00148341

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes