Evaluating the Effect of Itraconazole on Pathologic Complete Response Rates in Esophageal Cancer
A Phase II Trial Evaluating the Effectiveness of Itraconazole in Improving Pathologic Complete Response Rates in Patients With Esophageal Cancer Through Inhibition of the Hedgehog and AKT Signaling Pathways
1 other identifier
interventional
78
1 country
1
Brief Summary
Esophageal cancer, which has a low 5-year overall survival rate for all stages (\<20%) , is increasing in incidence. Previous studies have shown that the Hedgehog (Hh) and AKT signaling pathways are activated in a significant proportion of esophageal cancers. Itraconazole, a widely used anti-fungal medication, has been shown to inhibit various pathways involved in esophageal cancer tumorigenesis including Hh and AKT. In this phase II clinical trial, the investigators aim to evaluate the effect of itraconazole as a neoadjuvant therapy following standard of care chemoradiation in the treatment of locoregional esophageal and gastroesophageal junction carcinomas.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jun 2019
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 24, 2019
CompletedFirst Submitted
Initial submission to the registry
July 10, 2019
CompletedFirst Posted
Study publicly available on registry
July 15, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 24, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 29, 2026
November 4, 2021
November 1, 2021
7 years
July 10, 2019
November 2, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of pathological complete response with itraconazole
Generally for esophageal cancer the pathological complete response rate at time of esophagectomy is 25%, and we have designed our study with the projected number of patients assuming we observe an improvement of 15% or more in this rate following treatment with itraconazole. This is the study's primary endpoint. By inhibiting the Hh signaling pathway with the use of itraconazole, we anticipate improved pathological complete response rates.
3-4 months
Secondary Outcomes (3)
Comparison of hedgehog biomarkers before and after intervention
3-4 months
Comparison of phosphorylated VEGFR2 and AKT before and after intervention
3-4 months
Levels of itraconazole and metabolites in esophageal tissue
1 month.
Study Arms (1)
Itraconazole
EXPERIMENTALItraconazole capsule 300mg twice daily for 6-8 weeks following chemoradation.
Interventions
Oral administration of itraconazole twice daily from completion of neoadjuvant chemoradiation until esophagectomy.
Eligibility Criteria
You may qualify if:
- Patients diagnosed with localized (locoregional) esophageal cancer
- Patients diagnosed with localized (locoregional) gastroesophageal junction cancer
You may not qualify if:
- Patients unwilling or unable to provide informed consent
- Patients with QTc\>450ms
- Patients with a history of symptomatic congestive heart failure
- Patients with LFT's\>3xULN
- Patients who are pregnant
- Patients with a known allergy to itraconazole
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Dallas VA Medical Center
Dallas, Texas, 75216, United States
Related Publications (5)
Kim DJ, Kim J, Spaunhurst K, Montoya J, Khodosh R, Chandra K, Fu T, Gilliam A, Molgo M, Beachy PA, Tang JY. Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma. J Clin Oncol. 2014 Mar 10;32(8):745-51. doi: 10.1200/JCO.2013.49.9525. Epub 2014 Feb 3.
PMID: 24493717BACKGROUNDAntonarakis ES, Heath EI, Smith DC, Rathkopf D, Blackford AL, Danila DC, King S, Frost A, Ajiboye AS, Zhao M, Mendonca J, Kachhap SK, Rudek MA, Carducci MA. Repurposing itraconazole as a treatment for advanced prostate cancer: a noncomparative randomized phase II trial in men with metastatic castration-resistant prostate cancer. Oncologist. 2013;18(2):163-73. doi: 10.1634/theoncologist.2012-314. Epub 2013 Jan 22.
PMID: 23340005BACKGROUNDNacev BA, Grassi P, Dell A, Haslam SM, Liu JO. The antifungal drug itraconazole inhibits vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, trafficking, and signaling in endothelial cells. J Biol Chem. 2011 Dec 23;286(51):44045-44056. doi: 10.1074/jbc.M111.278754. Epub 2011 Oct 24.
PMID: 22025615BACKGROUNDKim 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.
PMID: 20385363BACKGROUNDChen 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.
PMID: 29592879BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David Wang, MD, PhD
North Texas Veterans Healthcare System
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- FED
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Staff Physician
Study Record Dates
First Submitted
July 10, 2019
First Posted
July 15, 2019
Study Start
June 24, 2019
Primary Completion (Estimated)
June 24, 2026
Study Completion (Estimated)
September 29, 2026
Last Updated
November 4, 2021
Record last verified: 2021-11