ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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

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.


Condition or disease Intervention/treatment Phase
Basal Cell Carcinoma (BCC) Skin Cancer Drug: Itraconazole Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Biomarker Trial to Evaluate the Efficacy of Itraconazole in Patients With Basal Cell Carcinomas
Study Start Date : April 2010
Actual Primary Completion Date : March 2011
Actual Study Completion Date : February 2012

Resource links provided by the National Library of Medicine


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
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

Experimental: Cohort B - Itraconazole 200 mg
Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months
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

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



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01108094


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Jean Y Tang, MD Stanford University

Publications of Results:
Responsible Party: Jean Yuh Tang, Associate Professor of Dermatology, Stanford University
ClinicalTrials.gov Identifier: NCT01108094     History of Changes
Other Study ID Numbers: IRB-17365
SU-04162010-5722 ( Other Identifier: Stanford University )
SKIN0004-TX ( Other Identifier: OnCore )
First Posted: April 21, 2010    Key Record Dates
Results First Posted: November 12, 2018
Last Update Posted: November 12, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Basal Cell
Skin Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Basal Cell
Neoplasms by Site
Skin Diseases
Itraconazole
Hydroxyitraconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors