Non-small Cell Lung Cancer Clinical Trial
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
Verified date | April 2021 |
Source | University of Texas Southwestern Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this study is to determine the pharmacodynamics effects of itraconazole in early-stage non-small cell lung cancer.
Status | Completed |
Enrollment | 13 |
Est. completion date | July 2018 |
Est. primary completion date | July 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
United States | UT Southwestern Medical Center | Dallas | Texas |
Lead Sponsor | Collaborator |
---|---|
University of Texas Southwestern Medical Center | United States Department of Defense |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Change in HIF1a From Baseline | A commercially available kit will be used to measure HIF1a levels. | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Change in VEGFR2 From Baseline | A commercially available kit will be used to measure VEGFR2 levels. | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Change in Phospho-VEGFR2 From Baseline | A commercially available kit will be used to measure Phospho-VEGFR2 levels. | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment | The following plasma cytokines were measured using a commercially available kit. | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Mean Percent Change in Angiogenic Cytokines From Baseline | A commercially available kit will be used to measure Angiogenic Cytokines levels. | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Changes in Perfusion (Ktrans) | DCE (dynamic contrast enhanced ) MRI is an established technology to assess microvessel density (MVD) and tumor capillary permeability. | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Number of Participants With Tumor SMO (Smoothened) Gene Mutations, GLI2 and CCND1 Copy Number, PI3K-mTOR Pathway Activation | phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (PI3K-mTOR pathway ) | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Change in Tumor Tissue GLI1, SHH and PTCH1 Levels From Baseline | This can be measured by analyzing frozen-treated tumor tissue for GLI1 (glioma-associated oncogene ) and PTCH1(patched-1) mRNA (Messenger Ribonucleic Acid) by qPCR. | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Change in Skin Biopsy GLI1 Levels From Baseline | We analyzed serial skin biopsies for GLI1 mRNA by qPCR (quantitative polymerase chain reaction). | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Change in Skin Biopsy SHH Levels From Baseline | We analyzed serial skin biopsies for SHH (Sonic Hedgehog )levels mRNA by qPCR. | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Change in Skin Biopsy PTCH1 Levels From Baseline | We analyzed serial skin biopsies for PTCH1 mRNA by qPCR. | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Number of Participants With Tumor Cell Proliferation/Apoptosis | Tumor proliferation and apoptosis will be assessed by tumor Ki67 and cleaved caspase 3 levels | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Itraconazole Levels in Post-treatment Serum | Itraconazole levels assessed by post-treatment serum | Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Itraconazole Levels in Tumor Tissue | Itraconazole levels assessed by tumor tissue | Baseline and Post Treatment (after 7-10 days of itraconazole bid) | |
Secondary | Itraconazole Levels in Skin Biopsy | Itraconazole levels assessed by skin biopsy | Baseline and Post Treatment (after 7-10 days of itraconazole bid) |
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