Ketoconazole in Treating Participants With Ongoing EGFR Inhibitor-Induced Rash

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Malignant Neoplasm
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Ketoconazole; Other: Placebo Administration

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 Type: Interventional
• Enrollment (Actual): 26
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Danville, Illinois, United States, 61832
      • Carle on Vermilion
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Louis Park, Minnesota, United States, 55426
      • Park Nicollet Frauenshuh Cancer Center
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (ketoconazole); Participants apply ketoconazole topically BID on days 1-28.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Ketoconazole; Applied topically; Other Names: Nizoral; Fungarest; Fungoral; Ketoderm; Ketoisdin; Orifungal M; Panfungol; R-41400; Xolegel
Placebo Comparator: Arm II (placebo); Participants apply placebo topically BID on days 1-28.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Placebo Administration; Applied topically

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Aminah Jatoi, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2018
• Primary Completion (Estimated): March 15, 2024
• Study Completion (Estimated): March 15, 2025

Study Registration Dates

• First Submitted: March 6, 2018
• First Submitted That Met QC Criteria: March 19, 2018
• First Posted (Actual): March 20, 2018

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Ketoconazole
• Other Study ID Numbers: MC17C1 (Other Identifier: Mayo Clinic in Rochester); P30CA015083 (U.S. NIH Grant/Contract); NCI-2018-00355 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA207183 (U.S. NIH Grant/Contract); 17-007786 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No