Itraconazole for Barrett's Esophagus

Overseen By Jill Torneden

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Kansas Medical Center

Must not be taking: CYP3A4 drugs

Disqualifiers: CHF, Liver dysfunction, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests itraconazole, a medication, to determine if it can prevent the recurrence of Barrett's esophagus (BE) after treatment. BE can lead to esophageal cancer if it returns, which occurs in many patients even after successful initial treatment. The trial compares two forms of itraconazole—a liquid solution and a capsule—to identify which might be more effective. Suitable candidates for this trial have Barrett's esophagus with specific conditions and plan to undergo endoscopic treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it excludes people with critical drug interactions with medications metabolized by cytochrome P450 (CYP)3A4. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that itraconazole is generally safe for humans. The FDA has already approved it to treat fungal infections like esophageal candidiasis, a fungal infection in the esophagus. This approval indicates prior use in people, providing some reassurance about its safety.

Common side effects of itraconazole include nausea, headache, and stomach pain, which are usually mild and resolve on their own. However, itraconazole can rarely cause serious side effects like liver or heart problems. Anyone considering joining the trial should discuss these risks with their doctor.

The trial for Barrett's esophagus uses both liquid and capsule forms of itraconazole. Both forms have similar safety records, but monitoring how the body reacts to any new treatment is important. Participants should maintain communication with the trial team and report any side effects they notice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about itraconazole for Barrett's Esophagus because it offers a novel approach by repurposing an antifungal medication for this condition. Unlike standard treatments that focus on acid suppression, itraconazole may work by impacting molecular pathways involved in esophageal cell changes. The trial explores two forms of delivery—solution and capsule—potentially offering flexibility and improved patient adherence compared to existing therapies. This unique mechanism and delivery method could lead to more effective management of Barrett's Esophagus, sparking interest in its potential benefits.

What evidence suggests that itraconazole might be an effective treatment for Barrett's esophagus?

Research suggests that itraconazole might help prevent the recurrence of Barrett's esophagus (BE). Studies have shown that itraconazole can block certain processes in the body that lead to BE. It has also slowed the growth of esophageal cancer cells in some cases. Additionally, animal studies have demonstrated that itraconazole can reduce the development of esophageal adenocarcinoma, a type of cancer. This trial tests both the solution and capsule forms of itraconazole to determine if they can prevent BE from returning after initial treatment. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with Barrett's esophagus who may have low to high-grade dysplasia or early-stage cancer and are set for endoscopic treatment. They should be relatively active (ECOG 0-2). It's not for those unable to consent, with severe heart failure, liver issues, allergy to itraconazole, pregnant women, or those on certain other drugs.

Inclusion Criteria

Patients with Barrett's esophagus with either confirmed low-grade dysplasia or high grade dysplasia or intramucosal/T1 adenocarcinoma (see histologic review) being considered for endoscopic treatment. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria

Rewritten Criteria: - You cannot understand and agree to participate in the study. - You have severe heart failure. - Your liver function tests are three times higher than normal. - You are allergic to itraconazole. - You are pregnant. - Your heart's electrical system has a prolonged QTc, which can be dangerous. - The medication you are taking interacts badly with the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive itraconazole in either solution or capsule form to prevent recurrent Barrett's esophagus

8-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of itraconazole effects on angiogenesis and molecular pathways

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Itraconazole

Trial Overview The study tests Itraconazole in capsule and solution forms as a preventive treatment against the recurrence of Barrett's Esophagus after initial successful therapy. The goal is to improve long-term outcomes by preventing relapse which could lead to cancer.

How Is the Trial Designed?

Group I: Itraconazole in solution form Active Control 1 Intervention

Participants in this arm will receive the solution form of itraconazole

Group II: Itraconazole in capsule form Active Control 1 Intervention

Participants in this arm will receive the capsule form of itraconazole

Itraconazole is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Sporanox for:

• Fungal infections
• Histoplasmosis
• Aspergillosis
• Blastomycosis

Approved in European Union as Sporanox for:

• Fungal infections
• Histoplasmosis
• Aspergillosis
• Blastomycosis

Approved in Canada as Sporanox for:

• Fungal infections
• Histoplasmosis
• Aspergillosis
• Blastomycosis

Approved in Japan as Sporanox for:

• Fungal infections
• Histoplasmosis
• Aspergillosis
• Blastomycosis

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

University of Texas, Southwestern Medical Center at Dallas

Collaborator

Trials

18

Recruited

21,200+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05609253

Itraconazole to Prevent Recurrent Barrett's Esophagus Itraconazole drug and blood levels, The primary endpoint will be the tissue (in esophageal biopsies) and blood concentrations of itraconazole. 8-12 months after ...

2. withpower.com withpower.com/trial/phase-1-barrett-oesophagitis-with-dysplasia-8-2022-19e7c

Itraconazole for Barrett's Esophagus · Info for Participants Trial Overview The study tests Itraconazole in capsule and solution forms as a preventive treatment against the recurrence of Barrett's Esophagus after initial ...

3. withpower.com withpower.com/clinical-trials/for-barretts-esophagus

Top Barrett's Esophagus Clinical Trials | Power This phase II trial tests how well itraconazole works in combination with standard of care endoscopy with ablation for the prevention of esophageal cancer ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31290765/

Targeting the Hedgehog Pathway Using Itraconazole to ... Itraconazole significantly decreases EAC development and SHH expression in a preclinical animal model of BM. In humans, BE tissue expresses ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12182032/

Systematic mapping of registered interventional studies ... What is the long-term effectiveness of endoscopic treatment (radiofrequency ablation) for precancerous Barrett's oesophagus or early cancers?

6. mayoclinic.org mayoclinic.org/drugs-supplements/itraconazole-oral-route/description/drg-20071421

Itraconazole (oral route) - Side effects & dosage Itraconazole is used to treat serious fungal or yeast infections. Itraconazole oral solution is only used to treat oropharyngeal or esophageal candidiasis ( ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/020083s061,020657s036lbl.pdf

SPORANOX (itraconazole) Capsules BOXED WARNING ... Limited data on the safety of long-term use (>6 months) of. SPORANOX. ®. Oral Solution are available at this time. The recommended dosage of SPORANOX. ®. Oral ...

8. go.drugbank.com go.drugbank.com/drugs/DB01167

Itraconazole: Uses, Interactions, Mechanism of Action Itraconazole is rapidly absorbed after oral administration. As oral capsules, peak plasma concentrations of itraconazole are reached within two to five hours.

9. rxlist.com rxlist.com/sporanox-drug.htm

Sporanox (Itraconazole Capsules): Side Effects, Uses, ... Limited data on the safety of long-term use (>6 months) of SPORANOX® Oral Solution are available at this time. The recommended dosage of SPORANOX® Oral ...