Itraconazole + Ablation for Preventing Esophageal Cancer

Not yet recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents, CYP3A4 drugs

Disqualifiers: Heart failure, QT prolongation, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding itraconazole, a drug typically used to treat fungal infections, can enhance the effectiveness of a common procedure for preventing esophageal cancer in individuals with high-risk Barrett's esophagus. Barrett's esophagus occurs when the esophagus lining changes, increasing cancer risk. Participants will receive either itraconazole or a placebo alongside a standard treatment called radiofrequency ablation, which uses heat to remove abnormal tissue. Individuals diagnosed with Barrett's esophagus with a certain level of abnormal cell changes might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer prevention.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on medications that interact with itraconazole, you may need to stop, switch, or adjust the dose. This will be decided on a case-by-case basis by the trial investigators.

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

Studies have shown that itraconazole, a drug typically used to treat fungal infections, has undergone safety testing in people. Research indicates that itraconazole is generally well-tolerated for these infections, though it can cause side effects like many medications. Some individuals have reported mild issues such as nausea or an upset stomach.

In cancer prevention studies, itraconazole has been tested in smaller groups for this new use. These studies suggest that while itraconazole can cause side effects, they are usually manageable. No major safety concerns emerged in these trials. It is important to note that this trial is in an early stage, so researchers are closely monitoring safety and side effects.

Overall, existing data suggests that itraconazole is reasonably safe, but potential side effects should always be considered and discussed with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for preventing esophageal cancer?

Researchers are excited about combining itraconazole with radiofrequency ablation for preventing esophageal cancer because itraconazole, typically an antifungal medication, may have anti-cancer properties. This combination could enhance the effectiveness of standard ablation techniques by potentially inhibiting cancer cell growth through itraconazole’s unique mechanism. Unlike the standard treatment options that primarily focus on ablating cancerous tissue, this approach adds a systemic treatment that may prevent the progression of precancerous conditions into full-blown cancer.

What evidence suggests that itraconazole combined with ablation might be effective for preventing esophageal cancer in high-risk Barrett's esophagus?

Research has shown that itraconazole, a drug typically used for fungal infections, might help prevent esophageal cancer by reducing the recurrence of Barrett's esophagus (BE). Itraconazole appears to work by decreasing the activity of certain genes that promote cell growth, potentially slowing cancer progression. Studies suggest that itraconazole can lower the risk of developing esophageal adenocarcinoma (EAC), a type of cancer, by affecting the Hedgehog pathway, which plays a crucial role in cancer growth. Due to its safety and affordability, itraconazole is considered a promising option for preventing BE from progressing to cancer. In this trial, one group of participants will receive itraconazole, while another group will receive a placebo. Early research in humans indicated that itraconazole might enhance the effectiveness of treatments like radiofrequency ablation, which uses heat to remove abnormal tissue. ^{1 2 3 4 5}

Who Is on the Research Team?

Ajay Bansal

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with high-risk Barrett's Esophagus, a condition where the esophagus lining becomes more like intestinal tissue, increasing esophageal cancer risk. Participants must be eligible for standard care endoscopy with ablation.

Inclusion Criteria

Absolute neutrophil count ≥ 1,000/microliter

Platelets ≥ 100,000/microliter

Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) ≤ 1.5 × institutional upper limit of normal

Exclusion Criteria

I have severe heart failure (NYHA class III or IV).

Participants may not be receiving any other investigational agents

Breastfeeding should be discontinued if the mother is treated with itraconazole

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive itraconazole or placebo orally twice daily for 6 weeks per cycle, with endoscopy and radiofrequency ablation

12 weeks

Multiple visits for endoscopy and ablation

Follow-up

Participants are monitored for safety, effectiveness, and recurrence of Barrett's esophagus

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Itraconazole
• Radiofrequency Ablation

Trial Overview The trial tests itraconazole, an antifungal drug, combined with radiofrequency ablation via endoscopy to prevent esophageal cancer in those at high risk due to Barrett's Esophagus. It compares this combination against standard ablation therapy alone.

How Is the Trial Designed?

Group I: Arm I (itraconazole) Experimental Treatment 6 Interventions

Patients receive itraconazole PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo 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: Arm II (placebo) Placebo Group 6 Interventions

Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo 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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ultrasound-guided radiofrequency ablation (RFA) significantly reduced the size of metastatic well-differentiated thyroid carcinoma tumors in 10 patients, with the mean diameter decreasing from 13.8 mm to 3.3 mm after treatment.

RFA was effective in controlling tumor growth in patients who could not undergo surgery, with 83% of tumors treated in a single session and a notable decrease in serum thyroglobulin levels in 7 out of 10 patients, indicating a positive response to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locoregional control of metastatic well-differentiated thyroid cancer by ultrasound-guided radiofrequency ablation. Baek, JH., Kim, YS., Sung, JY., et al.[2022]

The study of 90 radiofrequency ablation (RFA) procedures for benign thyroid nodules showed a learning curve in operator experience, with significant improvements in technique efficacy (TE) and volume reduction ratio (VRR) observed between the first 30 procedures and the next 30, indicating that operator experience positively impacts treatment outcomes.

The procedure was found to be safe, with only three minor complications reported, all of which resolved with conservative treatment, confirming that RFA for benign thyroid nodules is a low-risk intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Learning curve for radiofrequency ablation of benign thyroid nodules. Russ, G., Ben Hamou, A., Poirée, S., et al.[2021]

Radiofrequency ablation (RFA) is a safe and effective treatment for benign thyroid nodules, achieving an average volume reduction ratio of 84.11% in a study of 302 nodules from 236 patients.

The procedure resulted in significant volume reduction, with 91.06% of nodules showing more than 50% reduction and 27.81% completely disappearing, while complications were generally mild, including pain and transient voice changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiofrequency ablation of benign thyroid nodules: safety and imaging follow-up in 236 patients. Jeong, WK., Baek, JH., Rhim, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8492513/

Itraconazole Exerts Its Antitumor Effect in Esophageal ... We found itraconazole treatment led to significant reduction of CDK1, CDK2, CDK4 and E2F1 gene expression in OE33, FLO-1, KYSE70, and KYSE510 cells as shown in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05609253

Itraconazole to Prevent Recurrent Barrett's Esophagus A study record that includes the summary results posted in the ClinicalTrials.gov results database. Summary results information includes participant flow, ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS4212

Repurposing itraconazole for secondary prevention of ... Given its safety and affordability, itraconazole represents a promising strategy to reduce BE recurrence and EAC risk. Methods: This randomized, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05563766

A Phase II Trial to Evaluate the Effect of Itraconazole on ... This study will evaluate whether the use of itraconazole leads to increased rates of pathologic complete response (pathCR) by at least 15% compared to ...

5. journals.lww.com journals.lww.com/annalsofsurgery/Fulltext/10.1097/SLA.0000000000003455

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 higher SHH, Indian ...