Ketoconazole in Treating Participants With Ongoing EGFR Inhibitor-Induced Rash

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Supportive Care
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: March 15, 2024

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.

Interventions

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

Arms, Groups and Cohorts

  • Experimental: Arm I (ketoconazole)
    • Participants apply ketoconazole topically BID on days 1-28.
  • Placebo Comparator: Arm II (placebo)
    • Participants apply placebo topically BID on days 1-28.

Clinical Trial Outcome Measures

Primary Measures

  • Proportion of patients who report an improvement in skin rash
    • Time Frame: 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 Measures

  • Incidence of skin toxicity
    • Time Frame: Up to 4 weeks
    • 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.
  • Incidence of skin toxicity
    • Time Frame: 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
    • Time Frame: 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mayo Clinic
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Aminah Jatoi, M.D., Principal Investigator, Mayo Clinic

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