Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients w/ Basal Cell Carcinomas

Skin Cancer Clinical Trial

Official title:

Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients With Basal Cell Carcinomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01108094
• Other study ID #: IRB-17365
• Secondary ID: SU-04162010-5722
• Status: Completed
• Phase: Phase 2
• Start date: April 2010
• Est. completion date: February 2012

Study information

• Verified date: November 2018
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Basal cell carcinomas (BCCs) are the most common human cancer in the US and affect over 1 million people. There is no effective drug to prevent basal cell carcinomas of the skin.

We hope to learn if an oral anti-fungal drug, itraconazole, might inhibit a marker of proliferation and a biomarker (tumor signaling pathway) of BCC development.

Itraconazole is an FDA-approved drug for the treatment of fungal infections of the skin, and has been used for the past 25 years with relatively few side effects. It has been shown in mice to reduce a BCC biomarker and to reduce growth of BCCs.

Thus, it may reduce BCC growth in humans.

Description:

Participants with at least one BCC tumor measuring 4 mm or greater in diameter will be enrolled onto 1 of 2 treatment cohorts to receive oral itraconazole.

• Cohort A - 400 mg itraconazole (as 200 mg twice daily for 30 days), stratified by:

• Cohort A1 - Participants are vismodegib-naive.

• Cohort A2 - Participants had received prior vismodegib treatment.

• Cohort B - 200 mg itraconazole (as 100 mg twice daily, for up to 4 months). The objective of this cohort is to assess the anti-cancer efficacy of lower-dose extended treatment.

• Control Group - Tumors from untreated participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: February 2012
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA

• At least one BCC tumor (greater than 4 mm in diameter) at any skin location, to be biopsied and surgically removed.

• Had at least one liver function test [eg, aspartate aminotransferase (AST), alanine aminotransferase (ALT)] with normal results in the last year.

• Consent to research use of their BCC tissue.

• Cohort A or B: Willing to take itraconazole during the 2 to 3 weeks between biopsy and surgical removal of BCC

EXCLUSION CRITERIA

• History or current hepatitis or other liver disease.

• Currently taking systemic medications that would affect BCC tumors (oral retinoids) or metabolism of itraconazole (anti-convulsants, corticosteroids)

• History or current evidence of malabsorption or liver disease within the one year prior to enrollment.

• History or current evidence of hyperthyroidism increasing metabolism of itraconazole

• Unable to attend to 2nd study visit at Stanford for Mohs surgical excision

• Current immunosuppression disease (cancer, autoimmune disease)

• Receiving immunosuppressive drugs

• Pregnant

• Lactating

• Any female actively trying to become pregnant

Related Conditions & MeSH terms

• Basal Cell Carcinoma (BCC)
• Carcinoma
• Carcinoma, Basal Cell
• Skin Cancer
• Skin Neoplasms

Intervention

Drug:
• Itraconazole
Cohort A: oral itraconazole 400 mg as 200 mg twice daily; for 1 month Cohort B: oral itraconazole 200 mg as 100 mg twice daily; for up to 3 months

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ki67 Tumor Proliferation Biomarker	Percent change in Ki67 tumor proliferation biomarker was assessed at baseline and after 1 month of treatment, for Cohort A1 (vismodegib-naïve participants receiving 400 mg as 200 mg twice daily) vs control patients. The outcome is expressed as the % change from baseline of cells with a positive signal after staining for Ki67.; Paired analysis of tumors shows percent change between baseline (prior to treatment) and post itraconazole treatment in individual patients, & is reported as the mean of the changes observed for those lesions for which both baseline and treated valued are available.; Unpaired analysis shows percent change between individual tumors from control patients and itraconazole treated patients, and is reported as the change in mean of the group of baseline basal cell carcinoma (BCC) lesion measurements and the group of treated BCC lesion measurements.	1 month
Secondary	Change of GLI1 Tumor Biomarker	Tumor biomarker GLI1 (glioma-associated oncogene 1), part of the Hedgehog (HH) pathway, was assessed in vismodegib-naïve participants at baseline and after 1 month of treatment by quantitative polymerase chain reaction (qPCR). The relative expression of the biomarker was measured as the fold increase of GLI1 expression compared to that of housekeeping gene hypoxanthine-guanine phosphoribosyltransferase (HPRT), and the outcome was assessed as the percent change from the mean of the pre-treatment measurements to the mean of the post-treatment measurements. A negative mean indicates an overall reduction in GLI1 expression.	1 month
Secondary	Tumor Size	Tumor size was assessed by caliper measurement of the longest perpendicular diameters before and after itraconazole treatment, and determination of tumor area by multiplication of the measurements for each tumor. The outcome is expressed as the mean percent change in tumor area from baseline, with standard deviation. A negative value indicates a reduction in size.	Up to 3 months
Secondary	Tumor Response	The following criteria for basal cell carcinoma (BCC) tumor response were used.; Complete response (CR) means no visible evidence of any lesion consistent with BCC; Partial response (PR) means less than CR, but there was a visible decrease in BCC tumor size; No response (NR) / Stable Disease (SD) means no visible decrease in BCC tumor size; Progressive disease (PD) means an increase in size or number of BCC tumor lesions; Treatment assessment was conducted on the basis of lesion photographs by a dermatologist investigator who was blinded to the assigned treatment.	End of treatment period: 1 month (Cohort A) or 2.3 months (mean for Cohort B)