Itraconazole + Ablation for Preventing Esophageal Cancer

Recruiting at 6 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

64 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well itraconazole works in combination with standard of care endoscopy with ablation for the prevention of esophageal cancer in patients with high-risk Barrett's esophagus (BE). BE is a condition in which the lining of the esophagus changes. The tissue that lines the esophagus 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. It belongs to the family of drugs called antifungal agents. 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.

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.

What data supports the effectiveness of the treatment Itraconazole + Ablation for preventing esophageal cancer?

Radiofrequency ablation (RFA), a part of the treatment, has been shown to be effective and safe for treating thyroid nodules and thyroid cancer, suggesting it could be beneficial in other contexts as well. ^{1 2 3 4 5}

Is radiofrequency ablation (RFA) safe for treating thyroid conditions?

Radiofrequency ablation (RFA) has been shown to be generally safe for treating benign thyroid nodules and thyroid cancer recurrences, with complications like pain, hematoma (bruising), and temporary voice changes being relatively rare. ^{6 7 8 9 10}

How does the drug itraconazole differ from other treatments for preventing esophageal cancer?

Itraconazole is unique because it is an antifungal drug that also has anti-inflammatory properties, which may help in preventing esophageal cancer when combined with ablation (a procedure that removes abnormal tissue). This combination is novel as it leverages itraconazole's ability to enhance drug absorption and its broad activity spectrum, which is not typical for standard cancer prevention treatments. ^{11 12 13 14 15}

Research Team

Ajay Bansal

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

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

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

Platelets ≥ 100,000/microliter

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Locoregional control of metastatic well-differentiated thyroid cancer by ultrasound-guided radiofrequency ablation. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Learning curve for radiofrequency ablation of benign thyroid nodules. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Ultrasound-guided radiofrequency ablation (RFA) of benign symptomatic thyroid nodules - initial UK experience. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Radiofrequency Ablation for Iatrogenic Thyroid Artery Pseudoaneurysm: Initial Experience. [2017]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Radiofrequency Ablation on Autonomously Functioning Thyroid Nodules: A Critical Appraisal and Review of the Literature. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Sequential treatment by polidocanol and radiofrequency ablation of large benign partially cystic thyroid nodules with solid components: Efficacy and safety. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ultrasound-Guided Radiofrequency Ablation for Benign Nonfunctional Thyroid Nodules in Children: A Retrospective Study of 62 Patients with Over Four Years of Follow-Up. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Effect of Hashimoto's thyroiditis on the extent of the ablation zone in early stages of ultrasound-guided radiofrequency ablation for papillary thyroid microcarcinoma: a large cohort study of 772 patients. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Radiofrequency ablation of benign thyroid nodules: safety and imaging follow-up in 236 patients. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of radiofrequency ablation for treating locoregional recurrence from papillary thyroid cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Itraconazole (Sporanox) in superficial and systemic fungal infections. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Improved Bioavailability of Poorly Water-Soluble Drug by Targeting Increased Absorption through Solubility Enhancement and Precipitation Inhibition. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Bioavailability of itraconazole in rats and rabbits after administration of tablets containing solid dispersion particles. [2019]

14. United States pubmed.ncbi.nlm.nih.gov

Itraconazole therapy in lymphangitic and cutaneous sporotrichosis. [2013]

15. United States pubmed.ncbi.nlm.nih.gov

A randomized, double-blind comparison of itraconazole oral solution and fluconazole tablets in the treatment of esophageal candidiasis. [2019]