Barrett Oesophagitis With Dysplasia
Conditions
Keywords
Barrett's esophagus
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
Interventions
DRUGItraconazole in capsule form
Patients with high-risk BE will receive two weeks of itraconazole in the capsule form (N=5).
DRUGItraconazole in solution form
Patients with high-risk BE will receive two weeks of itraconazole in the solution form (N=5).
Sponsors
University of Kansas Medical Center
University of Texas, Southwestern Medical Center at Dallas
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
The primary purpose is to determine the ideal formulation (capsule versus solution) of itraconazole in this short-term pilot study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed