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

NCT06732388 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NCI-2024-10070UMI23-16-01P30CA046592UG1CA242632
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 6

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Time to complete eradication of intestinal metaplasia (CEIM) in days

  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 Outcomes (5)

• Time to complete eradication of 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

  At 12 months after CEIM

• Incidence of adverse events

  Up to 30 days after the end of intervention

• Correlate levels of itraconazole and its primary metabolite hydroxyitraconazole

  After two weeks of itraconazole

• Biosocial impact

  At baseline and at the end of the study

Other Outcomes (2)

• Correlation of the degree of inhibition of Hh, PI3K-AKT, and VEGFR2 signaling pathways with treatment response

  After two weeks of study drug administration

• Expression of cancer stem cell markers such as LGR5/CD44/DCAMKL1

  After two weeks of itraconazole

Study Arms (2)

Group I (itraconazole)

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Endoscopic Procedure; Drug: Itraconazole; Other: Questionnaire Administration; Procedure: Radiofrequency Ablation

Group II (placebo)

PLACEBO COMPARATOR

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Endoscopic Procedure; Drug: Placebo Administration; Other: Questionnaire Administration; Procedure: Radiofrequency Ablation

Interventions

Biopsy Procedure PROCEDURE

Undergo tissue biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Group I (itraconazole); Group II (placebo)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Group I (itraconazole); Group II (placebo)

Endoscopic Procedure PROCEDURE

Undergo endoscopy

Also known as: Endoscopic Examination, Endoscopy, ES

Group I (itraconazole); Group II (placebo)

Placebo Administration DRUG

Given PO

Group II (placebo)

Questionnaire Administration OTHER

Ancillary studies

Group I (itraconazole); Group II (placebo)

Radiofrequency Ablation PROCEDURE

Undergo radiofrequency ablation

Also known as: Ablation, Radiofrequency, Radiofrequency Interstitial Ablation, RFA

Group I (itraconazole); Group II (placebo)

Itraconazole DRUG

Given PO

Also known as: Lozanoc, Oriconazole, R 51,211, Sporanox

Group I (itraconazole)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

NOT YET RECRUITING

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Case Western Reserve University

Cleveland, Ohio, 44106, United States

NOT YET RECRUITING

Baylor University Medical Center

Dallas, Texas, 75246, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Barrett Esophagus; Adenocarcinoma Of Esophagus

Interventions

Biopsy; Specimen Handling; Endoscopy; Itraconazole; Radiofrequency Ablation

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Minimally Invasive Surgical Procedures; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Radiofrequency Therapy; Therapeutics; Ablation Techniques

Study Officials

• Ajay Bansal, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants as well as the study team will be blinded to the study drug assignment. The study endoscopist will be blinded to the treatment group to avoid bias. Will ensure that the laboratory personnel running the assays are blinded to the allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2024
• First Posted: December 13, 2024
• Study Start: June 23, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

US (6)