Itraconazole to Prevent Recurrent Barrett's Esophagus

Barrett Oesophagitis With Dysplasia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05609253
• Other study ID #: 00148341
• Status: Recruiting
• Phase: Phase 1
• Start date: September 14, 2022
• Est. completion date: December 2023

Study information

• Verified date: November 2022
• Source: University of Kansas Medical Center
• Contact: Jill Torneden
• Phone: 9135740533
• Email: jtorneden2[@]kumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Barrett Esophagus
• Barrett Oesophagitis With Dysplasia
• Esophagitis

Intervention

Drug:
• Itraconazole in capsule form
Patients with high-risk BE will receive two weeks of itraconazole in the capsule form (N=5).
• Itraconazole in solution form
Patients with high-risk BE will receive two weeks of itraconazole in the solution form (N=5).

Locations

Country	Name	City	State
United States	University of Kansas Medical Center	Kansas City	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
University of Kansas Medical Center	University of Texas, Southwestern Medical Center at Dallas

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Effects of itraconazole on Gli1 expression	Reduction in Gli1 expression	8-12 months after study initiation
Secondary	Effects of itraconazole on (Patched) PTCH expression	Reduction in PTCH expression by IHC	8-12 months after study initiation
Secondary	Effects of itraconazole on AKT pathway	Reduction in Phospho S6 by IHC	8-12 months after study initiation
Secondary	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