Itraconazole to Prevent Recurrent Barrett's Esophagus

Phase 1

Active, not recruiting

• Conditions: Barrett Oesophagitis With Dysplasia
• Interventions: Drug: Itraconazole in solution form; Drug: Itraconazole in capsule form

• Registration Number: NCT05609253
• Lead Sponsor: University of Kansas Medical Center

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-14
• Study First Submitted: 2022-09-26
• Study First Submitted QC: 2022-11-01
• Study First Posted: 2022-11-08
• Primary Completion: 2024-02-23
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-10
• Last Update Posted: 2024-10-15
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Itraconazole in solution form	Itraconazole in solution form	Participants in this arm will receive the solution form of itraconazole
Itraconazole in capsule form	Itraconazole in capsule form	Participants in this arm will receive the capsule form of itraconazole

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States