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

NCT ID: NCT06732388

Last Updated: 2026-01-30

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-16
• Study Completion Date: 2028-01-02

Brief Summary

This phase II trial tests how well itraconazole works in combination with the usual standard of care endoscopy with ablation for the prevention of esophageal cancer in patients who have high-risk Barrett's esophagus (BE). BE is a condition in which the lining of the esophagus changes and becomes more like the tissue that lines the intestine. People with Barrett's esophagus have a higher risk of developing esophageal cancer. Itraconazole is a drug used to prevent or treat fungal infections. Ablation refers to the removal of abnormal tissue using heat. Endoscopy is a procedure for looking at the esophagus using a long, flexible tube called an endoscope, which has a video camera at the end. Radiofrequency ablation is a type of heat therapy that uses radiofrequency energy (similar to microwave heat) to destroy the abnormal tissue in the esophagus. Giving itraconazole in combination with standard of care endoscopy with ablation may improve the effects of ablation and prevent esophageal cancer in patients with high-risk Barrett's esophagus.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate if itraconazole in the peri-ablation period in participants with high-risk Barrett's esophagus (BE) can accelerate BE regression i.e., achieve complete resolution of intestinal metaplasia (CRIM) faster than the control group.

SECONDARY OBJECTIVES:

I. To measure the time to event of complete eradication of dysplasia (CED). II. To measure the rate of BE recurrence during routine follow-up. III. To determine the safety and tolerability of itraconazole in participants with high-risk BE.

IV. To correlate levels of itraconazole and its primary metabolite hydroxyitraconazole in plasma and esophageal tissues with treatment response.

V. To compare biosocial impact on the participants in the itraconazole and control arms.

EXPLANATORY OBJECTIVE:

I. To correlate the degree of inhibition of Hedgehog (Hh), PI3K-AKT, and VEGFR2 signaling pathways with treatment response.

EXPLORATORY OBJECTIVES:

I. To determine whether expression (baseline and magnitude of change) of stem cell markers such as LGR5/CD44/DCAMKL1 can predict treatment response.

II. To bank blood samples and tissue biopsies for future analyses to understand the determinants of response.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive itraconazole orally (PO) twice daily (BID) on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles as long as there is an absence of disease progression or unacceptable toxicity. Patients undergo usual standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study.

GROUP II: Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles as long as there is an absence of disease progression or unacceptable toxicity. Patients undergo usual standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study.

After completion of study treatment, patients are followed up at 12 months.

Conditions

Barrett Esophagus; Clinical Stage I Esophageal Adenocarcinoma AJCC v8; Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8; Esophageal Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Group I (itraconazole)

Patients receive itraconazole PO twice daily (BID) on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles as long as there is an absence of disease progression or unacceptable toxicity. Patients undergo usual standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study.

Group Type: EXPERIMENTAL

Biopsy Procedure

Intervention Type: PROCEDURE

Undergo tissue biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Endoscopic Procedure

Intervention Type: PROCEDURE

Undergo endoscopy

Itraconazole

Intervention Type: DRUG

Given PO

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Radiofrequency Ablation

Intervention Type: PROCEDURE

Undergo radiofrequency ablation

Group II (placebo)

Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles as long as there is an absence of disease progression or unacceptable toxicity. Patients undergo usual standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study.

Group Type: PLACEBO_COMPARATOR

Biopsy Procedure

Intervention Type: PROCEDURE

Undergo tissue biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Endoscopic Procedure

Intervention Type: PROCEDURE

Undergo endoscopy

Placebo Administration

Intervention Type: DRUG

Given PO

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Radiofrequency Ablation

Intervention Type: PROCEDURE

Undergo radiofrequency ablation

Interventions

Biopsy Procedure

Undergo tissue biopsy

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Endoscopic Procedure

Undergo endoscopy

Intervention Type: PROCEDURE

Itraconazole

Given PO

Intervention Type: DRUG

Placebo Administration

Given PO

Intervention Type: DRUG

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Radiofrequency Ablation

Undergo radiofrequency ablation

Intervention Type: PROCEDURE

Other Intervention Names

Biopsy; BIOPSY_TYPE; Bx; Biological Sample Collection; Biospecimen Collected; Specimen Collection; Endoscopic Examination; Endoscopy; ES; Lozanoc; Oriconazole; R 51,211; Sporanox; Ablation, Radiofrequency; Radiofrequency Interstitial Ablation; RFA

Eligibility Criteria

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 adequate contraception (hormonal or barrier method of birth control; abstinence) two months prior to study entry, 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ajay Bansal, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Locations

University of Kansas Cancer Center

Kansas City, Kansas, United States

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Case Western Reserve University

Cleveland, Ohio, United States

Baylor University Medical Center

Dallas, Texas, United States

Countries

United States

Facility Contacts

Ajay Bansal

Role: primary

abansal@kumc.edu

816-861-4700

David Wang

Role: primary

davhwang@med.umich.edu

734-232-4594

Paul E. Wise

Role: primary

wisepe@wustl.edu

314-454-7177

Nicholas J. Shaheen

Role: primary

nshaheen@med.unc.edu

919-966-7047

Amitabh Chak

Role: primary

Amitabh.chak@uhhospitals.org

216-286-0151

Vani Konda

Role: primary

vani.konda@bswhealth.org

469-800-7050

Other Identifiers

NCI-2024-10070

Identifier Type: REGISTRY

Identifier Source: secondary_id

UMI23-16-01

Identifier Type: OTHER

Identifier Source: secondary_id

UMI23-16-01

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA046592

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1CA242632

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2024-10070

Identifier Type: -

Identifier Source: org_study_id