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

NCT01108094 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-17365SU-04162010-5722SKIN0004-TX
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Basal Cell Carcinoma (BCC); Skin Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  1 month

Secondary Outcomes (3)

• Change of GLI1 Tumor Biomarker

  1 month

• Tumor Size

  Up to 3 months

• Tumor Response

  End of treatment period: 1 month (Cohort A) or 2.3 months (mean for Cohort B)

Study Arms (3)

Cohort A - Itraconazole 400 mg

EXPERIMENTAL

Oral itraconazole 400 mg as 200 mg twice daily, for 1 month, stratified by prior vismodegib history

Drug: Itraconazole

Cohort B - Itraconazole 200 mg

EXPERIMENTAL

Oral itraconazole 200 mg as 100 mg twice daily, for up to 3 months

Drug: Itraconazole

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

Interventions

Itraconazole DRUG

* 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

Also known as: Sporanox

Cohort A - Itraconazole 400 mg; Cohort B - Itraconazole 200 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• 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.

  PMID: 24493717 RESULT

MeSH Terms

Conditions

Carcinoma, Basal Cell; Skin Neoplasms

Interventions

Itraconazole

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Results Point of Contact

• Title: Jean Tang MD PhD, Associate Professor of Dermatology
• Organization: Stanford University Medical Center

tangy@stanford.edu

650-723-6316

Study Officials

• Jean Y Tang, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Dermatology

Study Record Dates

• First Submitted: April 19, 2010
• First Posted: April 21, 2010
• Study Start: April 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: February 1, 2012
• Last Updated: November 13, 2018
• Results First Posted: November 13, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)