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| ID | Type | Description | Link |
|---|---|---|---|
| SU-04162010-5722 | Other Identifier | Stanford University | |
| SKIN0004-TX | Other Identifier | OnCore |
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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.
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 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A - Itraconazole 400 mg | Experimental | Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, stratified by prior vismodegib history |
|
| Cohort B - Itraconazole 200 mg | Experimental | Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months |
|
| Untreated Control | No Intervention | Patients otherwise eligible but unwilling to take itraconazole were enrolled onto the control arm of the study and received no treatment |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Itraconazole | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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.
| 1 month |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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INCLUSION CRITERIA
EXCLUSION CRITERIA
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| Name | Affiliation | Role |
|---|---|---|
| Jean Y Tang, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University School of Medicine | Stanford | California | 94305 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24493717 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A1 - Itraconazole 400 mg (Vismodegib-naïve) | Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, for participants without prior vismodegib treatment (vismodegib-naïve) and more than 1 lesion at baseline. |
| FG001 | Cohort A2 - Itraconazole 400 mg (Prior Vismodegib) | Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, for participants with prior vismodegib treatment, and more than 1 lesion at baseline. |
| FG002 | Cohort B - Itraconazole 200 mg | Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months |
| FG003 | Untreated Control | Participants otherwise eligible but unwilling to take itraconazole were enrolled onto the control arm of the study and received no treatment |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Patients with one or more BCC tumors measuring 4 mm or greater in diameter were enrolled.
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A1 - Itraconazole 400 mg (Vismodegib-naïve) | Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, for participants without prior vismodegib treatment (vismodegib-naïve) and more than 1 lesion at baseline. |
| BG001 | Cohort A2 - Itraconazole 400 mg (Prior Vismodegib) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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.
| Ki67 tumor proliferation biomarker assessment was not performed for Cohorts A2 (itraconazole 400 mg & prior vismodegib) and B (itraconazole 100 mg twice daily). | Posted | Mean | Standard Deviation | Mean percent change | 1 month | Basal Cell Carcinoma (BCC) lesions | Basal Cell Carcinoma (BCC) lesions |
2.3 months (average)
All patients treated with itraconazole were monitored for adverse events ≥ Grade 2. Only adverse events (AEs) grade 2 or greater were collected and reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort A1 - Itraconazole 400 mg +/- Prior Vismodegib | Oral itraconazole 400 mg as 200 mg twice daily, for 1 month. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Congestive heart failure | Cardiac disorders | Non-systematic Assessment | One grade 4 congestive heart failure occurred in a patient who had undiagnosed heart disease from prior adriamycin treatment for Hodgkin lymphoma 20 years previously. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Grade 2 Fatigue | General disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jean Tang MD PhD, Associate Professor of Dermatology | Stanford University Medical Center | 650-723-6316 | tangy@stanford.edu |
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| ID | Term |
|---|---|
| D002280 | Carcinoma, Basal Cell |
| D012878 | Skin Neoplasms |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| 1 month |
| 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 |
| Tumor Response | 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) |
| Withdrawal by Subject |
|
Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, for participants with prior vismodegib treatment, and more than 1 lesion at baseline. |
| BG002 | Cohort B - Itraconazole 200 mg (Vismodegib-naïve) | Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months treatment. All Cohort B participants were vismodegib-naïve. |
| BG003 | Untreated Control | Participants otherwise eligible but unwilling to take itraconazole were enrolled onto the control arm of the study and received no treatment |
| BG004 | Total | Total of all reporting groups |
| Basal cell carcinoma lesions |
|
| years |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants | Participants |
|
| Region of Enrollment | Number | participants | Participants |
|
| Number of Tumor Lesions at Baseline | Count of Participants | Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Cohort A1 - Itraconazole 400 mg (Vismodegib-naïve) | Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, for participants without prior vismodegib treatment (vismodegib-naïve) and more than 1 lesion at baseline. |
| OG001 | Cohort A2 - Itraconazole 400 mg (Prior Vismodegib) | Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, for participants with prior vismodegib treatment, and more than 1 lesion at baseline. |
| OG002 | Cohort B - Itraconazole 200 mg (Vismodegib-naïve) | Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months treatment. All Cohort B participants were vismodegib-naïve. |
| OG003 | Untreated Control | Participants otherwise eligible but unwilling to take itraconazole were enrolled onto the control arm of the study and received no treatment. |
|
|
|
| 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. | Analysis conducted for Cohorts A1 - Itraconazole 400 mg (Vismodegib-naive) and A2 - Itraconazole 400 mg (Prior Vismodegib) only. GLI1 tumor biomarker assessment was not performed for the Cohort B (100 mg twice daily); or Control Group. | Posted | Mean | Standard Deviation | Percent change | 1 month | Basal Cell Carcinoma (BCC) lesions | Basal Cell Carcinoma (BCC) lesions |
|
|
|
|
| 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. | Change in tumor area was assessed for only for Cohort A1 or B participants who had > 1 basal cell carcinoma (BCC) tumor (42 and 14 lesions respectively). No Cohort A2 participants had > 1 BCC tumor. No data were collected from untreated patients. | Posted | Mean | Standard Deviation | Mean percent change | Up to 3 months | Basal Cell Carcinoma (BCC) lesions | Basal Cell Carcinoma (BCC) lesions |
|
|
|
|
| Secondary | Tumor Response | 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. | Posted | Count of Participants | Participants | End of treatment period: 1 month (Cohort A) or 2.3 months (mean for Cohort B) |
|
|
|
| 0 |
| 12 |
| 1 |
| 12 |
| 1 |
| 12 |
| EG001 | Cohort A2 - Itraconazole 400 mg (Prior Vismodegib) | Oral itraconazole 400 mg as 200 mg twice daily, for 1 month. | 0 | 3 | 0 | 3 | 0 | 3 |
| EG002 | Cohort B - Itraconazole 200 mg (Vismodegib-naïve) | Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months treatment. All Cohort B participants were vismodegib-naïve. | 0 | 4 | 0 | 4 | 0 | 4 |
|
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| D018295 |
| Neoplasms, Basal Cell |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D010879 |
| Piperazines |
|
| Basal Cell Carcinoma (BCC) lesions |
|
| Basal Cell Carcinoma (BCC) lesions |
|
Average tumor size reductions were compared between Cohort A1 and Cohort B. |
| t-test, 1 sided |
| 0.435 |
| Other |
| Partial Response (PR) |
|
| No Response (NR) / Stable Disease (SD) |
|
| Disease Progression (PD) |
|