Ketoconazole in Treating Participants With Ongoing EGFR Inhibitor-Induced Rash

Early Phase 1

Active, not recruiting

• Conditions: Malignant Neoplasm
• Interventions: Drug: Ketoconazole; Other: Placebo Administration; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

• Registration Number: NCT03471364
• Lead Sponsor: Mayo Clinic

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2018-03-06
• Study First Submitted QC: 2018-03-19
• Study First Posted: 2018-03-20
• Study Start: 2018-09-25
• Primary Completion: 2024-09-15
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-03
• Study Completion: 2025-09-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 58

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (placebo)	Quality-of-Life Assessment	Participants apply placebo topically BID on days 1-28.
Arm II (placebo)	Placebo Administration	Participants apply placebo topically BID on days 1-28.
Arm II (placebo)	Questionnaire Administration	Participants apply placebo topically BID on days 1-28.
Arm I (ketoconazole)	Laboratory Biomarker Analysis	Participants apply ketoconazole topically BID on days 1-28.
Arm I (ketoconazole)	Quality-of-Life Assessment	Participants apply ketoconazole topically BID on days 1-28.
Arm II (placebo)	Laboratory Biomarker Analysis	Participants apply placebo topically BID on days 1-28.
Arm I (ketoconazole)	Questionnaire Administration	Participants apply ketoconazole topically BID on days 1-28.
Arm I (ketoconazole)	Ketoconazole	Participants apply ketoconazole topically BID on days 1-28.

Primary Outcome Measures

Name	Time	Method
Proportion of patients who report an improvement in skin rash	Up to 4 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of skin toxicity	Up to 4 weeks	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.
Incidence of adverse events for ketoconazole	Up to 4 weeks	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.

Trial Locations

Locations (6)

Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

Carle on Vermilion; 🇺🇸 Danville, Illinois, United States

Park Nicollet Frauenshuh Cancer Center; 🇺🇸 Saint Louis Park, Minnesota, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

Regions Hospital; 🇺🇸 Saint Paul, Minnesota, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States