Neoadjuvant Itraconazole in Non-small Cell Lung Cancer

NCT ID: NCT02357836

Last Updated: 2021-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2018-07-31

Brief Summary

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

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.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Itraconazole

600 mg twice daily for 10-14 days

Group Type: OTHER

Itraconazole

Intervention Type: DRUG

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 (pharmacokinetics) 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.

Interventions

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 (pharmacokinetics) 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.

Intervention Type: DRUG

Eligibility Criteria

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 (Eastern Cooperative Oncology Group) 0-2 performance status

5. Adequate organ function as defined below:

• total bilirubin within normal institutional limits
• AST (Aspartate Aminotransferase) (SGOT)/ALT (Alanine Aminotransferase) (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 (New York Heart Association) 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 (Creatinine clearance) < 45 mL/min (increased risk of nephrogenic systemic fibrosis [NSF] from MRI Gadolinium contrast).

12. Known allergy to MRI contrast.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

David E Gerber

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lorraine Pelosof, M.D.

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STU 122014-038

Identifier Type: -

Identifier Source: org_study_id