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Itraconazole as a Targeted Therapy for Inhibiting Hedgehog Pathway Signaling in Esophageal Cancer Patients

Primary Purpose

Esophageal Cancer

Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Itraconazole
Sponsored by
Dallas VA Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Esophageal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

• Clinical diagnosis of esophageal cancer, including gastroesophageal junction cancer

Exclusion Criteria:

  • Patients unwilling or unable to provide informed consent
  • Coagulopathy that precludes safe endoscopic/surgical procedure (platelet count <100,000/mm3, INR>1.5)
  • Esophageal varices
  • Comorbidity (e.g. pulmonary, cardiac, renal, or liver disease) that precludes safe participation in the study
  • QTc>450 ms
  • LFT's>3xULN
  • Pregnancy
  • Allergy to itraconazole
  • History of symptomatic congestive heart failure

Sites / Locations

  • Dallas VA Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Itraconazole

Arm Description

Itraconazole 300 mg po bid for 14-17 days

Outcomes

Primary Outcome Measures

Inhibition of Hedgehog pathway signaling as measured by real-time PCR.
mRNA expression levels as measured by real-time PCR of Hedgehog pathway ligands and target genes will be compared between baseline and post-itraconazole treatment.

Secondary Outcome Measures

Inhibition of VEGFR2 pathway signaling as measured by Western blot
Protein expression levels of phosphorylated VEGFR2 will be compared between baseline and post-itraconazole treatment.

Full Information

First Posted
April 14, 2016
Last Updated
November 2, 2021
Sponsor
Dallas VA Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT02749513
Brief Title
Itraconazole as a Targeted Therapy for Inhibiting Hedgehog Pathway Signaling in Esophageal Cancer Patients
Official Title
Feasibility of Itraconazole as a Targeted Therapy for Inhibition of Hedgehog Pathway Signaling in Patients With Esophageal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2016 (undefined)
Primary Completion Date
September 2019 (Actual)
Study Completion Date
October 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dallas VA Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to demonstrate that orally administered itraconazole, a commonly used antifungal medication, can inhibit Hedgehog pathway signaling in patients with esophageal cancer, including adenocarcinoma (EAC) and squamous cell carcinoma (ESCC).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer

7. Study Design

Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Itraconazole
Arm Type
Experimental
Arm Description
Itraconazole 300 mg po bid for 14-17 days
Intervention Type
Drug
Intervention Name(s)
Itraconazole
Primary Outcome Measure Information:
Title
Inhibition of Hedgehog pathway signaling as measured by real-time PCR.
Description
mRNA expression levels as measured by real-time PCR of Hedgehog pathway ligands and target genes will be compared between baseline and post-itraconazole treatment.
Time Frame
2-3 weeks
Secondary Outcome Measure Information:
Title
Inhibition of VEGFR2 pathway signaling as measured by Western blot
Description
Protein expression levels of phosphorylated VEGFR2 will be compared between baseline and post-itraconazole treatment.
Time Frame
2-3 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: • Clinical diagnosis of esophageal cancer, including gastroesophageal junction cancer Exclusion Criteria: Patients unwilling or unable to provide informed consent Coagulopathy that precludes safe endoscopic/surgical procedure (platelet count <100,000/mm3, INR>1.5) Esophageal varices Comorbidity (e.g. pulmonary, cardiac, renal, or liver disease) that precludes safe participation in the study QTc>450 ms LFT's>3xULN Pregnancy Allergy to itraconazole History of symptomatic congestive heart failure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Wang, MD, PhD
Organizational Affiliation
North Texas Veterans Healthcare System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dallas VA Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75216
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
24493717
Citation
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.
Results Reference
result
PubMed Identifier
23340005
Citation
Antonarakis 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.
Results Reference
result
PubMed Identifier
34376577
Citation
Zhang 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.
Results Reference
derived

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Itraconazole as a Targeted Therapy for Inhibiting Hedgehog Pathway Signaling in Esophageal Cancer Patients

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