Epidermal Growth Factor Receptor Inhibition for Keratinopathies

We will conduct the first interventional multi-site Phase 1/2a trial of low-dose erlotinib to test its safety and efficacy as systemic treatment of moderate-to-severe keratinopathies. The trial will have three parts: During Part A, the natural history of keratinopathies and baseline for scores will be determined through at least 8 weeks of observation. We will use the mean of scores for our baseline, rather than a static measure at baseline to account for potential variability without the intervention. Part B will be the dose escalation component, in which the subject will initiate 50 mg erlotinib,8 wks later escalate to 75 mg, and then 8 wks later to 100 mg erlotinib pending tolerance after each 8-week period. During this 24-week period, we will be assessing safety (Phase 1) in comparison to the 8-week baseline observation period (own control) and at ease dosing level. We will also evaluate efficacy based on dosing (Phase 2a) to achieve preliminary data to guide future trials if the use of erlotinib is a "go" based on safety. Part C is the open-label extension period. Each participant will decide on the continued dosing for the subsequent 6 months in shared decision making with the investigator based on tolerance and effect. In total, the study involves 1 year on the erlotinib treatment, although the primary endpoint is 6 months after initiation. The additional 6 months will allow for further observation for potential toxicity and possible improved effect after additional time on drug. Participants will be eligible to participate in the open-label treatment period only if they have maintained \>70% compliance with completion of studies during the initial 6 months.