Ketoconazole in Treating Participants With Ongoing EGFR Inhibitor-Induced Rash

Malignant Neoplasm Clinical Trial

Official title:

Double-Blinded, Placebo-Controlled Trial to Explore the Anti-Androgen, Ketoconazole, for Treating Patients With an Ongoing Epidermal Growth Factor Receptor (EGFR) Inhibitor-Induced Rash

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03471364
• Other study ID #: MC17C1
• Secondary ID: NCI-2018-00355MC
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: August 22, 2018
• Est. completion date: March 15, 2025

Study information

• Verified date: April 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This early phase I trial studies the side effects of ketoconazole and how well it works in treating participants with ongoing EGFR inhibitor-induced rash. Ketoconazole may reduce the symptoms related to EGFR inhibitor therapy and improve EGFR inhibitor-induced rash.

Description:

PRIMARY OBJECTIVES: I. To demonstrate that topical ketoconazole, an anti-androgen, palliates EGFR inhibitor-induced rash within a group of racially diverse cancer patients. II. To explore the role of ribonucleic acid (RNA) sequencing to identify other targets that might be used at a later date for rash palliation. III. To evaluate toxicities associated with topical ketoconazole. OUTLINE: Participants are randomized to 1 of 2 arms. ARM I: Participants apply ketoconazole topically twice daily (BID) on days 1-28. ARM II: Participants apply placebo topically BID on days 1-28. After completion of study treatment, participants are followed up at 1 week.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 26
• Est. completion date: March 15, 2025
• Est. primary completion date: June 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient has developed a rash or symptoms of a rash (cutaneous burning) characteristic of an EGFR inhibitor (health-care provider report of the rash with no other documentation is permitted)
• Patient is anticipated to continue for at least 28 days with an EGFR inhibitor or restart =< 14 days of registration and continue for at least 28 days
• Mayo only: Patient is willing to provide a skin biopsy for correlative research; Note:

Can be waived with permission of study chair (documentation such as an email must be provided)

• Patient must complete baseline quality of life (QOL) packet

Exclusion Criteria:

• Patient has a prior allergy or intolerance of ketoconazole
• Patient has an allergy or intolerance to sulfites

Related Conditions & MeSH terms

• Malignant Neoplasm
• Neoplasms

Intervention

Drug:
• Ketoconazole
Applied topically

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Placebo Administration
Applied topically
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Carle on Vermilion	Danville	Illinois
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Park Nicollet Frauenshuh Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	Carle Cancer Center	Urbana	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in PLA2G4D, PLOD2, and SALL4	Assessed by ribonucleic acid (RNA) sequencing. Will explore the association between baseline/change in PLA2G4D, PLOD2, and SALL4 with rash improvement. Baseline gene expression level and change from baseline in gene expression level for the androgen-related genes such as PLA2G4D, PLOD2, and SALL4 will be compared between arms by t-test and Wilcoxon rank sum procedures (as appropriate). Mixed Models for Logistic Regression will also be implemented to explore the association between PLA2G4D, PLOD2, and SALL4 with rash improvement by adjusting the baseline gene expression level and change from baseline in gene expression levels for each gene. Descriptive factors will be used as covariates in the modeling analysis.	Baseline up to 4 weeks
Primary	Proportion of patients who report an improvement in skin rash	Assessed by Skindex-16. Will be estimated using the cumulative incidence function with time to improvement defined as the time from randomization to the first of the two consecutive weeks of improved symptom. The cumulative incidence of rash improvement after 4 weeks of treatment will be summarized separately by treatment arm. The difference in rash improvement incidences will be estimated and will be compared using two-sample Z-test.	Up to 4 weeks
Secondary	Incidence of skin toxicity	As measured by the Skindex-16. Responses to the Skindex-16 will be categorized into three subscales: symptom, emotional, and functional. Analysis of the total scales and subscales of the Skindex-16 will involve a t-test and Wilcoxon rank sum procedures (as appropriate) at each time point as well as linear mixed modeling. Descriptive factors will be used as covariates in the modeling analysis. The change from baseline in the total score and subscales of the Skindex-16 will be compared between two arms by a two-sample, two-sided t-test. If there is evidence of non-normality (via Shapiro-Wilk testing), a non-parametric procedure such as Wilcoxon rank sum will be used.	Up to 4 weeks
Secondary	Incidence of skin toxicity	As measured by the Skin Toxicity Assessment Tool (STAT). Responses to the STAT will be categorized into three subscales: symptom, emotional, and functional. Analysis of the total scales and subscales of the STAT will involve a t-test and Wilcoxon rank sum procedures (as appropriate) at each time point as well as linear mixed modeling. Descriptive factors will be used as covariates in the modeling analysis. The change from baseline in the total score and subscales of the STAT will be compared between two arms by a two-sample, two-sided t-test. If there is evidence of non-normality (via Shapiro-Wilk testing), a non-parametric procedure such as Wilcoxon rank sum will be used.	Up to 4 weeks
Secondary	Incidence of adverse events for ketoconazole	Adverse events will be tabulated by treatment arm. Frequencies of various types of adverse events (AEs) will be compared using Fisher's exact test. Will explore the difference in reliability of the direct versus (vs.) indirect AE attribution approaches in the placebo arm.	Up to 4 weeks