Ketoconazole in Treating Participants With Ongoing EGFR Inhibitor-Induced Rash
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
PRIMARY OBJECTIVES:
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To demonstrate that topical ketoconazole, an anti-androgen, palliates EGFR inhibitor-induced rash within a group of racially diverse cancer patients.
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To explore the role of ribonucleic acid (RNA) sequencing to identify other targets that might be used at a later date for rash palliation.
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I (ketoconazole) Participants apply ketoconazole topically BID on days 1-28. |
Drug: Ketoconazole
Applied topically
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
Other: Questionnaire Administration
Ancillary studies
|
| Placebo Comparator: Arm II (placebo) Participants apply placebo topically BID on days 1-28. |
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Placebo Administration
Applied topically
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
Other: Questionnaire Administration
Ancillary studies
|
Outcome Measures
Primary Outcome Measures
- 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
- Incidence of skin toxicity [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 [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.
Other Outcome Measures
- Change in PLA2G4D, PLOD2, and SALL4 [Baseline up to 4 weeks]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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)
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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
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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)
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Patient must complete baseline quality of life (QOL) packet
Exclusion Criteria:
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Patient has a prior allergy or intolerance of ketoconazole
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Patient has an allergy or intolerance to sulfites
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Carle on Vermilion | Danville | Illinois | United States | 61832 |
| 2 | Carle Cancer Center | Urbana | Illinois | United States | 61801 |
| 3 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
| 4 | Park Nicollet Frauenshuh Cancer Center | Saint Louis Park | Minnesota | United States | 55426 |
| 5 | Regions Hospital | Saint Paul | Minnesota | United States | 55101 |
| 6 | University of Rochester | Rochester | New York | United States | 14642 |
Sponsors and Collaborators
- Mayo Clinic
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Aminah Jatoi, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MC17C1
- NCI-2018-00355
- MC17C1
- P30CA015083
- R01CA207183