Itraconazole in Combination With Ablation for the Prevention of Esophageal Cancer in Patients With High-risk Barrett's Esophagus

Inclusion Criteria: * Participants with history of prior esophagogastroduodenoscopy (EGD) with an established diagnosis of BE ≥ 2 cm with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD) or T1a esophageal adenocarcinoma (EAC), naïve to treatment, and being considered for ablation. * Note: An eligible diagnosis from an EGD outside of the enrollment sites is allowed for inclusion as long as the biopsies have been reviewed by two pathologists. The two pathologists could include a pathologist from the referring site and an institutional pathologist at the local enrolling site, two pathologists from the referring site, or two pathologists from the local enrolling site. The diagnosis between two pathologists has to be concordant regarding the presence of dysplasia or cancer. Discrepant diagnoses will be resolved by a third pathologist, if needed * Participants older than 18 years will be enrolled. Because the incidence of BE and related cancer is very low in participants \< 18 years of age, children are excluded from this study * Clinically eligible for EGD and endoscopic treatment of BE * Absolute neutrophil count ≥ 1,000/microliter * Platelets ≥ 100,000/microliter * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) * Note: Higher total bilirubin levels (≤ 3 mg/dL) can be allowed if due to known benign liver condition, i.e. Gilbert's * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 1.5 × institutional upper limit of normal * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Participants on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible * There are no controlled data on the effects of itraconazole on the developing human fetus at the recommended therapeutic dose. For this reason and because azoles are known to be teratogenic, women of child-bearing potential must agree to use one or more methods of highly effective contraception that do not contain estrogen (e.g. progestin only oral contraceptive, non-hormonal intrauterine device, bilateral tubal ligation) two months prior to study entry, for the duration of study participation and two months after completing the study drug. Women should not donate eggs or participate in in vitro fertilization for the duration of study participation, and two months after completing the study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. Male subjects should avoid donating sperm, and if engaged in intercourse with women of child-bearing potential use a method of highly effective contraception. * Activities of Reproductive Potential: In addition to heterosexual intercourse, activities that could lead to pregnancy (e.g. sperm or egg donation, participation in in vitro fertilization) should be considered when evaluating the reproductive potential of clinical trial subjects. * Females of Reproductive Potential: A non-post-menopausal female who has not had a bilateral oophorectomy or medically documented ovarian failure. A female who has had a tubal ligation sterilization, or hysterectomy would not be considered to be of reproductive potential unless participating in activities of reproductive potential other than heterosexual intercourse (e.g. egg donation, participation in in vitro fertilization). * Menopause: * Twelve (12) months of spontaneous amenorrhea or; * Spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels \> 40 mIU/mL or; * Subject is post-bilateral oophorectomy with or without hysterectomy * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Current New York Heart Association (NYHA) class III or IV congestive heart failure * Prolonged corrected QT (QTc) (\> 450 ms for men and \> 470 ms for women) * Participants may not be receiving any other investigational agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to itraconazole * Uncontrolled intercurrent illness., or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women are excluded from this study because itraconazole is a class C agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with itraconazole, breastfeeding should be discontinued if the mother is treated with itraconazole * Critical drug interactions (grades D or higher) with other medications metabolized by cytochrome P450(CYP)3A4 (if the medication cannot be discontinued or switched or dose modified); these decisions will be made on a case-by-case basis by the site investigators in consultation with the treating provider. Drug interactions can be assessed using one of the available on-line resources, for instance, UpToDate or Clinical Formulary and/or in collaboration with a clinical pharmacist. * Note: If there are potential drug interactions that do not exclude the participant from the study, a brief research note summarizing the decision-making process about potential drug interactions and their management will be required before the participants are enrolled in the trial * History of eosinophilic esophagitis * History of strictures not allowing passage of the radiofrequency ablation (RFA) assembly * Participants must not have evidence of active/recurrent invasive cancer of a non-esophageal organ * Participants with EAC greater than stage T1a * Persistent (\> 24 hour \[h\]) systolic blood pressure (BP) greater than or equal to 160 mmHg (to avoid reaching hypertensive crisis defined as systolic BP \> 180 mmHg) * Patients taking eliglustat. Co-administration of itraconazole and eliglustat is contraindicated in subjects that are poor or intermediate metabolizers of CYP2D6