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

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

The primary endpoint will be the tissue (in esophageal biopsies) and blood concentrations of itraconazole.

Reduction in Vascular endothelial growth factor (VEGF)/ Vascular endothelial growth factor receptor type 2 (VEGFR2) by IHC

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.