Itraconazole to Prevent Recurrent Barrett's Esophagus

Study Overview
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Brief Summary
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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

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

Conditions
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Barrett Oesophagitis With Dysplasia

Intervention / Treatment
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* Drug: Itraconazole in capsule form
* Drug: Itraconazole in solution form


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: The primary purpose is to determine the ideal formulation (capsule versus solution) of itraconazole in this short-term pilot study.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Barrett's esophagus