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

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ClinicalTrials.gov Identifier: NCT01108094
Recruitment Status : Completed
First Posted : April 21, 2010
Results First Posted : November 12, 2018
Last Update Posted : November 12, 2018
Sponsor:
Information provided by (Responsible Party):
Jean Yuh Tang, Stanford University

Tracking Information
First Submitted Date  ICMJE April 19, 2010
First Posted Date  ICMJE April 21, 2010
Results First Submitted Date November 22, 2016
Results First Posted Date November 12, 2018
Last Update Posted Date November 12, 2018
Study Start Date  ICMJE April 2010
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 9, 2018)
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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 20, 2010)
To determine if 3 weeks of oral or topical Itraconazole reduces BCC biomarkers (Gli1, the target gene of the Hedgehog pathway and Ki67, a marker of proliferation). [ Time Frame: 3 weeks ]
Change History Complete list of historical versions of study NCT01108094 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2018)
  • 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.
  • 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.
  • 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.
    • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2010)
To determine if topical Itraconazole penetrates BCC tumors. We will compare Itraconazole levels in excised BCC tumors/surrounding skin after 2-3 weeks of topical (400mg daily) vs. oral Itraconazole (400 mg daily). [ Time Frame: after 2-3 weeks of topical (400mg daily) vs. oral Itraconazole (400 mg daily) ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients w/ Basal Cell Carcinomas
Official Title  ICMJE Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients With Basal Cell Carcinomas
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.
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Basal Cell Carcinoma (BCC)
  • Skin Cancer
Intervention  ICMJE 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
Other Name: Sporanox
Study Arms
  • Experimental: Cohort A - Itraconazole 400 mg
    Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, stratified by prior vismodegib history
    Intervention: Drug: Itraconazole
  • Experimental: Cohort B - Itraconazole 200 mg
    Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months
    Intervention: Drug: Itraconazole
  • 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
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 9, 2018)
29
Original Estimated Enrollment  ICMJE
 (submitted: April 20, 2010)
30
Actual Study Completion Date February 2012
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01108094
Other Study ID Numbers  ICMJE IRB-17365
SU-04162010-5722 ( Other Identifier: Stanford University )
SKIN0004-TX ( Other Identifier: OnCore )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Jean Yuh Tang, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jean Y Tang, MD Stanford University
PRS Account Stanford University
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP