A Phase II Trial to Evaluate the Effect of Itraconazole on Pathologic Complete Response Rates in Resectable Esophageal Cancer

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Capable of giving informed consent
• Pathologic diagnosis of esophageal cancer (ESCC or EAC) or GEJ cancer deemed resectable by a surgeon with a plan to undergo neoadjuvant chemoradiation or perioperative chemoimmunotherapy and curative intent esophagectomy
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 at enrollment
• Adequate renal and liver function as judged by the treating physician

You cannot join if

• Inability to provide Informed Consent
• New York Heart Association (NYHA) class III or IV congestive heart failure (CHF)
• LFT>3X upper limit of normal
• Drug allergy to itraconazole
• Positive pregnancy test
• Those with QTc>450 milliseconds (ms) will have QTc monitored during therapy by serial EKG to ensure QTc does not lengthen to what the treating clinician considers significant

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

Treatments listed in the registry

• Itraconazole (Drug): Itraconazole 300 milligrams po bid for two weeks prior and 6-8 weeks after completion of standard of care neoadjuvant chemoradiation (or 4-6 weeks after completion of standard of care pre-operative chemoimmunotherapy)

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• biopsy: Part of the study plan
• CT scans: Part of the study plan
• PET scans: Part of the study plan
• endoscopy: Part of the study plan
• surgery: Part of the study plan

Main goals

• Rate of pathological complete response with itraconazole (20 weeks)

Other goals

• Comparison of Hedgehog, AKT, and angiogenesis pathway status before and after intervention
• Correlation of peripheral blood and esophageal tissue levels of itraconazole and hydroxyitraconazole with pathologic response
• Develop a predictive genomic profile of treatment response
• Determine the utility of ctDNA and exosome characterization as a prognostic marker

Planned enrollment: 78 (estimated).

• VA Palo Alto Health Care System, Palo Alto, CA, Palo Alto, California
• VA Ann Arbor Healthcare System, Ann Arbor, MI, Ann Arbor, Michigan
• Durham VA Medical Center, Durham, NC, Durham, North Carolina
• VA Portland Health Care System, Portland, OR, Portland, Oregon
• VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX, Dallas, Texas
• Michael E. DeBakey VA Medical Center, Houston, TX, Houston, Texas
• VA Puget Sound Health Care System Seattle Division, Seattle, WA, Seattle, Washington

Site status as of Oct 30, 2026. Check the live record before contacting a site.

These papers are listed in the registry record. Unless a paper is marked as about this trial, it is background research on the treatment or disease, not results from this study.

• Background research, not results from this trialZhang W, Bhagwath AS, Ramzan Z, Williams TA, Subramaniyan I, Edpuganti V, Kallem RR, Dunbar KB, Ding P, Gong K, Geurkink SA, Beg MS, Kim J, Zhang Q, Habib AA, Choi SH, Lapsiwala R, Bhagwath G, Dowell JE, Melton SD, Jie C, Putnam WC, Pham TH, Wang DH. Itraconazole Exerts Its Antitumor Effect in Esophageal Cancer By Suppressing the HER2/AKT Signaling Pathway. Mol Cancer Ther. 2021 Oct;20(10):1904-1915. doi: 10.1158/1535-7163.MCT-20-0638. Epub 2021 Aug 10.
• Background research, not results from this trialKim J, Tang JY, Gong R, Kim J, Lee JJ, Clemons KV, Chong CR, Chang KS, Fereshteh M, Gardner D, Reya T, Liu JO, Epstein EH, Stevens DA, Beachy PA. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell. 2010 Apr 13;17(4):388-99. doi: 10.1016/j.ccr.2010.02.027.
• Background research, not results from this trialChen MB, Liu YY, Xing ZY, Zhang ZQ, Jiang Q, Lu PH, Cao C. Itraconazole-Induced Inhibition on Human Esophageal Cancer Cell Growth Requires AMPK Activation. Mol Cancer Ther. 2018 Jun;17(6):1229-1239. doi: 10.1158/1535-7163.MCT-17-1094. Epub 2018 Mar 28.
• Background research, not results from this trialKelly RJ, Ansari AM, Miyashita T, Zahurak M, Lay F, Ahmed AK, Born LJ, Pezhouh MK, Salimian KJ, Ng C, Matsangos AE, Stricker-Krongrad AH, Mukaisho KI, Marti GP, Chung CH, Canto MI, Rudek MA, Meltzer SJ, Harmon JW. Targeting the Hedgehog Pathway Using Itraconazole to Prevent Progression of Barrett's Esophagus to Invasive Esophageal Adenocarcinoma. Ann Surg. 2021 Jun 1;273(6):e206-e213. doi: 10.1097/SLA.0000000000003455.

• ClinicalTrials.gov NCT05563766

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 8, 2026. Public record; not medical advice.