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Neoadjuvant Itraconazole in Non-small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02357836
Recruitment Status : Completed
First Posted : February 6, 2015
Last Update Posted : September 17, 2019
United States Department of Defense
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

Brief Summary:
The purpose of this study is to determine the pharmacodynamics effects of itraconazole in early-stage non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Itraconazole Early Phase 1

Detailed Description:

This is a phase 0 clinical trial. While clinical data including safety will be recorded, the principal outcomes are pharmacodynamic endpoints. Specifically, the investigators seek to identify: (1) effects of itraconazole on tumor angiogenesis, (2) effects of itraconazole on the Hh pathway, (3) biomarker predictors of these effects, (4) the correlation between itraconazole pharmacokinetics and these effects, (5) the correlation between different biomarkers.

Up to 15 eligible patients with previously diagnosed or suspected NSCLC planned for resection will undergo a study-specific core needle biopsy, imaging (dynamic contrast enhanced [DCE]-, diffusion weighted imaging [DWI]-, and arterial spin labeling [ASL] magnetic resonance imaging [MRI]), skin punch biopsy, and collection of peripheral blood. Subjects will then receive itraconazole 600 mg PO daily for 7-10 days, following which they will undergo repeat imaging, skin biopsy, and blood collection. Subsequently they will undergo surgical resection. Due to the safety profile of itraconazole when used as an antifungal agent , all histologic subtypes of NSCLC will be eligible for the trial. The itraconazole dose of 600 mg, higher than an anti-angiogenic dose, has been shown to inhibit the Hedgehog (Hh) pathway.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 0 Pharmacodynamic Study of the Effects of Itraconazole on Tumor Angiogenesis and the Hedgehog Pathway in Early-stage Non-small Cell Lung Cancer
Actual Study Start Date : June 2015
Actual Primary Completion Date : July 2018
Actual Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
600 mg twice daily for 10-14 days
Drug: Itraconazole
Once on study, itraconazole will be taken twice daily for a total of 10-14 days. After being on itraconazole for 7-10 days, "Post-treatment" assessments will include a skin biopsy, blood draw for the PK analyses and the cytokine panel, and also MRI evaluations (anticipated to last 45-50 minutes). Toxicity assessments and laboratory checks will also be conducted during that time. Following these assessments, itraconazole will be continued until the day of surgery. At the time of surgical resection, a tissue sample (with adjacent normal tissue as per standard resection technique) will be obtained to complete the analysis. Following resection, subjects will be followed per standard post-operative procedure.

Primary Outcome Measures :
  1. Change in Pharmacodynamics (assessed by changes in tumor tissue microvessel density [MVD]) [ Time Frame: Tumor Tissue will be collected: 1-Baseline prior to treatment 2-And Post Treatment (after 7-10 days of itraconazole bid) ]
    Determine the pharmacodynamic effects of itraconazole on tumor angiogenesis (assessed by changes in tumor tissue microvessel density [MVD])

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically or cytologically proven NSCLC planned for surgical resection. All NSCLC histologic subtypes are eligible. Alternatively, patients in whom a diagnosis of NSCLC is highly suspected based on history and imaging studies and who are, therefore, scheduled for diagnostic biopsy and/or surgical resection will also be eligible for screening, enrollment, and study treatment if they meet all additional eligibility criteria. In the event that biopsies do not confirm NSCLC, such patients will be removed from study but monitored for any adverse events resulting from study participation.
  2. No prior therapy but planned for surgical resection
  3. Age ≥ 18 years.
  4. ECOG 0-2 performance status
  5. Adequate organ function as defined below:

    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
    • creatinine ≤ 2 X institutional upper limit of normal
  6. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

    6.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

    • Has not undergone a hysterectomy or bilateral oophorectomy; or
    • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  7. Ability to understand and willingness to sign a written informed consent.

Exclusion Criteria:

  1. Subjects may not be receiving any investigational agents that would confound interpretation of study pharmacodynamic endpoints.
  2. History of allergic reactions attributed to itraconazole or to compounds of similar chemical or biologic composition to itraconazole.
  3. Uncontrolled, concurrent medical illness.
  4. Active hepatitis or symptomatic liver disease.
  5. History of or current evidence of uncontrolled cardiac ventricular dysfunction (congestive heart failure) or NYHA Class III or IV heart failure.
  6. Current use of medications significantly affecting metabolism of itraconazole (certain anti-convulsants, corticosteroids). See 3.5 Drug Interactions in protocol.
  7. Current evidence of hyperthyroidism (which would increase metabolism of itraconazole).
  8. Pregnant or lactating female or any female trying to get pregnant.
  9. Claustrophobia that would interfere with MRI studies anticipated to last 45-50 minutes.
  10. Metal implants deemed at risk for migration during MRI studies.
  11. CrCl < 45 mL/min (increased risk of nephrogenic systemic fibrosis [NSF] from MRI Gadolinium contrast).
  12. Known allergy to MRI contrast.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02357836

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United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
United States Department of Defense
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Principal Investigator: Lorraine Pelosof, M.D. UT Southwestern Medical Center
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Responsible Party: University of Texas Southwestern Medical Center Identifier: NCT02357836    
Other Study ID Numbers: STU 122014-038
First Posted: February 6, 2015    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors