Barrett EsophagusPhase 2NCT06732388
Itraconazole in Combination With Ablation for the Prevention of Esophageal Cancer in Patients With High-risk Barrett's Esophagus
A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Endoscopic Procedure in people with Barrett Esophagus and Clinical Stage I Esophageal Adenocarcinoma AJCC v8, run by National Cancer Institute (NCI) at 6 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Barrett Esophagus, Clinical Stage I Esophageal Adenocarcinoma AJCC v8, Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Endoscopic Procedure
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 6 sitesUnited States
- Study dates
- 23 Jun 2026to 1 Dec 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 6 recruiting
- Recruiting
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
David Wang, 734-232-4594, davhwang@med.umich.edu
David Wang
- Recruiting
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Nicholas J. Shaheen, 919-966-7047, nshaheen@med.unc.edu
Nicholas J. Shaheen
- Not yet recruiting
Case Western Reserve University
Cleveland, Ohio, 44106
Amitabh Chak, 216-286-0151, Amitabh.chak@uhhospitals.org
Amitabh Chak
- Recruiting
Baylor University Medical Center
Dallas, Texas, 75246
Vani Konda, 469-800-7050, vani.konda@bswhealth.org
Vani Konda
- Not yet recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Ajay Bansal, 816-861-4700, abansal@kumc.edu
Ajay Bansal
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Paul E. Wise, 314-454-7177, wisepe@wustl.edu
Paul E. Wise
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- To compare biosocial impact on the participants in the itraconazole and control arms.
EXPLANATORY OBJECTIVE:
- To correlate the degree of inhibition of Hedgehog (Hh), PI3K-AKT, and VEGFR2 signaling pathways with treatment response.
EXPLORATORY OBJECTIVES:
- 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
- Being tested
- Biopsy Procedure, Biospecimen Collection, Endoscopic Procedure, Itraconazole, Placebo Administration
- Medical subject headings
- Barrett Esophagus, Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo tissue biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Endoscopic ProcedureProcedure or surgery
Also called Endoscopic Examination, Endoscopy, ES
Undergo endoscopy
ItraconazoleDrug
Also called Lozanoc, Oriconazole, R 51,211, Sporanox
Given PO
Placebo AdministrationDrug
Given PO
Questionnaire AdministrationOther
Ancillary studies
Radiofrequency AblationProcedure or surgery
Also called Ablation, Radiofrequency, Radiofrequency Interstitial Ablation, RFA
Undergo radiofrequency ablation
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Endoscopic Procedure; Drug: Placebo Administration; Other: Questionnaire Administration; Procedure: Radiofrequency Ablation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: At 12 months after CEIM
Incidence of adverse events
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.
Measured: Up to 30 days after the end of intervention
Correlate levels of itraconazole and its primary metabolite hydroxyitraconazole
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.
Measured: After two weeks of itraconazole
Biosocial impact
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.
Measured: At baseline and at the end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2024
- Study start23 Jun 2026
- Primary completion1 Aug 2030 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Barrett EsophagusStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ajay Bansal, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06732388
- Sponsor's protocol ID
- NCI-2024-10070
- Other IDs
- NCI-2024-10070, UMI23-16-01, UMI23-16-01, P30CA046592, UG1CA242632
- Status last verified
- Jul 2026
- First submitted
- 12 Dec 2024
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.