Back to resultsPilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients w/ Basal Cell Carcinomas
Primary Purpose
Basal Cell Carcinoma (BCC), Skin Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Itraconazole
Sponsored by
About this trial
This is an interventional treatment trial for Basal Cell Carcinoma (BCC)
Eligibility Criteria
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
Sites / Locations
- Stanford University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
No Intervention
Arm Label
Cohort A - Itraconazole 400 mg
Cohort B - Itraconazole 200 mg
Untreated Control
Arm Description
Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, stratified by prior vismodegib history
Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months
Patients otherwise eligible but unwilling to take itraconazole were enrolled onto the control arm of the study and received no treatment
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01108094
Brief Title
Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients w/ Basal Cell Carcinomas
Official Title
Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients With Basal Cell Carcinomas
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
February 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Basal Cell Carcinoma (BCC), Skin Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A - Itraconazole 400 mg
Arm Type
Experimental
Arm Description
Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, stratified by prior vismodegib history
Arm Title
Cohort B - Itraconazole 200 mg
Arm Type
Experimental
Arm Description
Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months
Arm Title
Untreated Control
Arm Type
No Intervention
Arm Description
Patients otherwise eligible but unwilling to take itraconazole were enrolled onto the control arm of the study and received no treatment
Intervention Type
Drug
Intervention Name(s)
Itraconazole
Other Intervention Name(s)
Sporanox
Intervention Description
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
Primary Outcome Measure Information:
Title
Ki67 Tumor Proliferation Biomarker
Description
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.
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Change of GLI1 Tumor Biomarker
Description
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.
Time Frame
1 month
Title
Tumor Size
Description
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.
Time Frame
Up to 3 months
Title
Tumor Response
Description
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.
Time Frame
End of treatment period: 1 month (Cohort A) or 2.3 months (mean for Cohort B)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean Y Tang, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24493717
Citation
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: 10.1200/JCO.2013.49.9525. Epub 2014 Feb 3.
Results Reference
result
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Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients w/ Basal Cell Carcinomas
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