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

July 28, 2026 updated by: National Cancer Institute (NCI)

Repurposing Itraconazole for Secondary Prevention of Metaplasia and Primary Prevention of Cancer in Patients With High-risk Barrett's Esophagus in Combination With Ablation

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 eradication of intestinal metaplasia (CEIM) 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.

Study Type

Interventional

Enrollment (Estimated)

76

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Not yet recruiting
        • University of Kansas Cancer Center
        • Principal Investigator:
          • Ajay Bansal
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Rogel Cancer Center
        • Principal Investigator:
          • David Wang
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Paul E. Wise
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • UNC Lineberger Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Nicholas J. Shaheen
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Not yet recruiting
        • Case Western Reserve University
        • Contact:
        • Principal Investigator:
          • Amitabh Chak
    • Texas
      • Dallas, Texas, United States, 75246
        • Not yet recruiting
        • Baylor University Medical Center
        • Contact:
        • Principal Investigator:
          • Vani Konda

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Drug: Itraconazole
Given PO
Other Names:
  • Sporanox
  • Lozanoc
  • Oriconazole
  • R 51,211
Procedure: Endoscopic Procedure
Undergo endoscopy
Other Names:
  • ES
  • Endoscopy
  • Endoscopic Examination
Procedure: Radiofrequency Ablation
Undergo radiofrequency ablation
Other Names:
  • RFA
  • Ablation, Radiofrequency
  • Radiofrequency Interstitial Ablation
Procedure: Biopsy Procedure
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy
Placebo Comparator: 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.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Drug: Placebo Administration
Given PO
Procedure: Endoscopic Procedure
Undergo endoscopy
Other Names:
  • ES
  • Endoscopy
  • Endoscopic Examination
Procedure: Radiofrequency Ablation
Undergo radiofrequency ablation
Other Names:
  • RFA
  • Ablation, Radiofrequency
  • Radiofrequency Interstitial Ablation
Procedure: Biopsy Procedure
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to complete eradication of intestinal metaplasia (CEIM) in days
Time Frame: Between day 1, cycle 1 (1 cycle = 6 weeks) and the date of endoscopy at which the participant is deemed to reach CEIM
CEIM will be defined based on the absence of visible Barrett's esophagus (BE) and invisible BE (i.e., no intestinal metaplasia [IM] in biopsies of the gastroesophageal junction and the cardia). Will be reported descriptively. Will compare the unadjusted hazard rates between the itraconazole and control groups using log rank test.
Between day 1, cycle 1 (1 cycle = 6 weeks) and the date of endoscopy at which the participant is deemed to reach CEIM

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: Up to 30 days after the end of intervention
Will be assessed by National Cancer Institutes Common Terminology Criteria for Adverse Events version 5.0 criteria to document adverse events and measure specific laboratory parameters to monitor for the safety and tolerability of itraconazole and assessed by descriptive statistics.
Up to 30 days after the end of intervention
Correlate levels of itraconazole and its primary metabolite hydroxyitraconazole
Time Frame: After two weeks of itraconazole
Will be assessed in plasma and esophageal tissues with treatment response. Will measure these metabolites after two weeks of itraconazole therapy by obtaining biopsies of the esophagus. These measurements will be correlated with biomarker and clinical response to understand how tissue levels of the drug change the molecular and primary endpoints. Will also measure the blood levels to test the feasibility of blood levels for prediction of clinical response in the future.
After two weeks of itraconazole
Biosocial impact
Time Frame: At baseline and at the end of the study
Will be assessed by questionnaires to collect information about the biosocial endpoints. These will include cancer-specific distress questionnaire, Gastrointestinal Symptom Rating Scale, Health-Related Quality of life short form 12 version 2, and Patient-Reported Outcomes Measurement Information System anxiety and depression scores as previously used at the beginning and at the end of the study. The summary measures such as mean or median of these distress scores will be compared between arms using t-test (or Wilcoxon rank test in case of non normality). Linear regression models will be used for studying the differences in the average distress scores between arms adjusted for age, sex and prior history of anxiety or depression.
At baseline and at the end of the study
Time to complete eradication of dysplasia
Time Frame: Between day 1, cycle 1 (1 cycle = 6 weeks) and the date of endoscopy at which surveillance biopsies do not show dysplasia
Will be assessed by surveillance biopsies at the time of the endoscopy that documents CEIM and the biopsies at the time of first surveillance endoscopy will be evaluated for dysplasia.
Between day 1, cycle 1 (1 cycle = 6 weeks) and the date of endoscopy at which surveillance biopsies do not show dysplasia
Rate of BE recurrence over follow-up
Time Frame: At 12 months after CEIM
Will be assessed between the study treatment group and the control group. BE recurrence will be defined as histologic presence of IM (with or without dysplasia) in biopsies from the tubular esophagus or in biopsies at the gastroesophageal junction. The results from the standard of care endoscopy closest to the 12-month time point after CEIM will be used to collect information for this endpoint.
At 12 months after CEIM

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of the degree of inhibition of Hh, PI3K-AKT, and VEGFR2 signaling pathways with treatment response
Time Frame: After two weeks of study drug administration
Measures will be assessed in biopsies of the gastroesophageal junction as well as in biopsy of BE after two weeks of study drug administration by histological techniques.
After two weeks of study drug administration
Expression of cancer stem cell markers such as LGR5/CD44/DCAMKL1
Time Frame: After two weeks of itraconazole
Measures will be assessed in biopsies of the gastroesophageal junction as well as biopsies of BE after two weeks of study drug administration by histological techniques.
After two weeks of itraconazole

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Ajay Bansal, MD, University of Kansas Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 23, 2026

Primary Completion (Estimated)

August 1, 2030

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

December 12, 2024

First Submitted That Met QC Criteria

December 12, 2024

First Posted (Actual)

December 13, 2024

Study Record Updates

Last Update Posted (Actual)

July 29, 2026

Last Update Submitted That Met QC Criteria

July 28, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2024-10070 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P30CA046592 (U.S. NIH Grant/Contract)
  • UG1CA242632 (U.S. NIH Grant/Contract)
  • UMI23-16-01 (Other Identifier: DCP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe