Itraconazole to Prevent Recurrent Barrett's Esophagus

Sponsor

University of Kansas Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05609253

Collaborator

University of Texas, Southwestern Medical Center at Dallas (Other)

Enrollment

Location

Arms

14.6

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Barrett Oesophagitis With Dysplasia	Drug: Itraconazole in capsule form Drug: Itraconazole in solution form	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

The primary purpose is to determine the ideal formulation (capsule versus solution) of itraconazole in this short-term pilot study.The primary purpose is to determine the ideal formulation (capsule versus solution) of itraconazole in this short-term pilot study.

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Sep 14, 2022

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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).

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).

Outcome Measures

Primary Outcome Measures

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

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 Gli1 expression [8-12 months after study initiation]
Reduction in Gli1 expression
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kansas Medical Center	Kansas City	Kansas	United States	66160

Sponsors and Collaborators

University of Kansas Medical Center
University of Texas, Southwestern Medical Center at Dallas

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Kansas Medical Center

ClinicalTrials.gov Identifier:

NCT05609253

Other Study ID Numbers:

00148341

First Posted:

Nov 8, 2022

Last Update Posted:

Nov 8, 2022

Last Verified:

Nov 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by University of Kansas Medical Center

Barrett's esophagus

Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 8, 2022