Neoadjuvant Itraconazole in Non-small Cell Lung Cancer

NCT02357836 | Completed Early Phase 1 Results DMC

• 1 other identifier: STU 122014-038
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Changes in Tumor Tissue Microvessel Density [MVD] From Baseline

  Images of DAPI (4',6-Diamidino-2-Phenylindole) , CD31 (cluster of differentiation 31 ), and CD34 (cluster of differentiation 34) were taken from the same field of view and then merged.

  Baseline and Post Treatment (after 7-10 days of itraconazole bid)

Secondary Outcomes (15)

• Change in HIF1α From Baseline

  Baseline and Post Treatment (after 7-10 days of itraconazole bid)

• Change in VEGFR2 From Baseline

  Baseline and Post Treatment (after 7-10 days of itraconazole bid)

• Change in Phospho-VEGFR2 From Baseline

  Baseline and Post Treatment (after 7-10 days of itraconazole bid)

• Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment

  Baseline and Post Treatment (after 7-10 days of itraconazole bid)

• Mean Percent Change in Angiogenic Cytokines From Baseline

  Baseline and Post Treatment (after 7-10 days of itraconazole bid)

Study Arms (1)

Itraconazole

OTHER

600 mg twice daily for 10-14 days

Drug: Itraconazole

Interventions

Itraconazole 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.

Itraconazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• No prior therapy but planned for surgical resection
• Age ≥ 18 years.
• ECOG (Eastern Cooperative Oncology Group) 0-2 performance status
• 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
• 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.
• 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).
• Ability to understand and willingness to sign a written informed consent.

You may not qualify if:

• Subjects may not be receiving any investigational agents that would confound interpretation of study pharmacodynamic endpoints.
• History of allergic reactions attributed to itraconazole or to compounds of similar chemical or biologic composition to itraconazole.
• Uncontrolled, concurrent medical illness.
• Active hepatitis or symptomatic liver disease.
• 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.
• Current use of medications significantly affecting metabolism of itraconazole (certain anti-convulsants, corticosteroids). See 3.5 Drug Interactions in protocol.
• Current evidence of hyperthyroidism (which would increase metabolism of itraconazole).
• Pregnant or lactating female or any female trying to get pregnant.
• Claustrophobia that would interfere with MRI studies anticipated to last 45-50 minutes.
• Metal implants deemed at risk for migration during MRI studies.
• CrCl (Creatinine clearance) \< 45 mL/min (increased risk of nephrogenic systemic fibrosis \[NSF\] from MRI Gadolinium contrast).
• Known allergy to MRI contrast.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• United States Department of Defense: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Itraconazole

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Results Point of Contact

• Title: Dr. David Gerber
• Organization: UT Southwestern Medical Center

David.Gerber@UTSouthwestern.edu

214-648-4180

Study Officials

• Lorraine Pelosof, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 15, 2015
• First Posted: February 6, 2015
• Study Start: June 1, 2015
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: May 3, 2021
• Results First Posted: May 3, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)