Ketoconazole in Treating Participants With Ongoing EGFR Inhibitor-Induced Rash

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Malignant Neoplasm

Intervention / Treatment
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* Drug: Ketoconazole
* Other: Laboratory Biomarker Analysis
* Other: Placebo Administration
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (ketoconazole)<br>Participants apply ketoconazole topically BID on days 1-28. | Drug: Ketoconazole<br>* Applied topically<br>* Other names: Xolegel;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Placebo Comparator: Arm II (placebo)<br>Participants apply placebo topically BID on days 1-28. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Placebo Administration<br>* Applied topically<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 |