Clinical trial NCT01108094: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Basal Cell Carcinoma (BCC)
Skin Cancer
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2010-04-21
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Ki67 Tumor Proliferation Biomarker
timeFrame: 1 month
Secondary outcomes:
measure: Change of GLI1 Tumor Biomarker
timeFrame: 1 month
measure: Tumor Size
timeFrame: Up to 3 months
measure: Tumor Response
timeFrame: End of treatment period: 1 month (Cohort A) or 2.3 months (mean for Cohort B)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Jean Y Tang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.