- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01108094
Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients w/ Basal Cell Carcinomas
Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients With Basal Cell Carcinomas
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
Stanford, California, United States, 94305
- Stanford University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort A - Itraconazole 400 mg
Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, stratified by prior vismodegib history
|
Other Names:
|
Experimental: Cohort B - Itraconazole 200 mg
Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months
|
Other Names:
|
No Intervention: Untreated Control
Patients otherwise eligible but unwilling to take itraconazole were enrolled onto the control arm of the study and received no treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ki67 Tumor Proliferation Biomarker
Time Frame: 1 month
|
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.
|
1 month
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change of GLI1 Tumor Biomarker
Time Frame: 1 month
|
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
|
Tumor Size
Time Frame: Up to 3 months
|
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
|
Tumor Response
Time Frame: End of treatment period: 1 month (Cohort A) or 2.3 months (mean for Cohort B)
|
The following criteria for basal cell carcinoma (BCC) tumor response were used.
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)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jean Y Tang, MD, Stanford University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Neoplasms, Basal Cell
- Carcinoma
- Carcinoma, Basal Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Antifungal Agents
- Steroid Synthesis Inhibitors
- 14-alpha Demethylase Inhibitors
- Itraconazole
Other Study ID Numbers
- IRB-17365
- SU-04162010-5722 (Other Identifier: Stanford University)
- SKIN0004-TX (Other Identifier: OnCore)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Skin Cancer
-
University of HawaiiVA Palo Alto Health Care SystemCompletedCancer, Other Than Non-melanoma Skin CancerUnited States
-
EnlundCompletedBreast Cancer | Skin Cancer | Colo-rectal CancerSweden
-
McMaster UniversityRecruitingSkin Cancer, Basal Cell Skin Cancer Skin Cancer, Non-Melanoma Skin Cancers - Squamous Cell Carcinoma Patient SatisfactionCanada
-
SciBase ABRecruitingKeratinocyte Skin CancerGermany
-
Rutgers, The State University of New JerseyCompleted
-
University of MichiganBlue Cross Blue Shield of Michigan FoundationCompletedSkin Cancer PreventionUnited States
-
Fox Chase Cancer CenterNational Cancer Institute (NCI)CompletedSkin Cancer PreventionUnited States
-
Xoft, Inc.Eminence Clinical Research, Inc.UnknownNonmelanoma Skin CancerUnited States
-
Assistance Publique - Hôpitaux de ParisRecruitingSkin Cancer, Non-MelanomaFrance
-
Technische Universität DresdenCompletedNon-melanoma Skin CancerGermany
Clinical Trials on Itraconazole
-
University of Maryland, BaltimoreCompleted
-
University of Alabama at BirminghamWashington University School of Medicine; University of California, DavisCompletedInvasive Fungal InfectionsUnited States, Panama
-
Johns Hopkins UniversityMemorial Sloan Kettering Cancer CenterCompleted
-
University of Kansas Medical CenterUniversity of Texas, Southwestern Medical Center at DallasRecruitingBarrett Oesophagitis With DysplasiaUnited States
-
Halcygen Pharmaceuticals LimitedCompletedOnychomycosisUnited States
-
H. Lundbeck A/SCompletedCytochrome P450 InteractionUnited Kingdom, United States
-
Sara BotrosCompleted
-
Pulmatrix Inc.Completed
-
Stiefel, a GSK CompanyGlaxoSmithKlineCompletedOnychomycosisUnited States, South Africa, Canada, Dominican Republic, Ecuador, Honduras, Panama
-
Sidney Kimmel Comprehensive Cancer Center at Johns...TerminatedNon-small Cell Lung Cancer MetastaticUnited States