Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06545695
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-06
Brief Title:
Epidermal Growth Factor Receptor Inhibition for Keratinopathies
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Epidermal Growth Factor Receptor Inhibition for Keratinopathies
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Epidermal growth factor receptor EGFR signaling plays a key role in regulating epidermal cell proliferation survival and differentiation Keratins form a scaffold with epidermal desmosomes that involves ErbB EGFR signaling and keratin deficiency makes keratinocytes more sensitive to EGFR activation Erlotinib an EGFR inhibitor was approved 20 years ago for cancer treatment and is generally used at 150 mg daily in adults 50 kg While gastrointestinal and cutaneous side effects commonly occur at doses of 150 mg adverse events occur less often at lower doses We first reported erlotinib as effective for Olmsted syndrome a rare hereditary EDD with painful PPK that results from variants in TRPV3 Erlotinib is now the treatment of choice for children and adults with Olmsted syndrome Erlotinib is thought to inhibit formation of a complex that includes TRPV3 EGFR and its primary skin-based ligand TGF-a which in turn regulates keratinocyte proliferation and differentiation High-throughput screening to identify compounds that stabilize keratin filaments have also pointed to the EGFR pathway for targeting Reviews and recent case reports have suggested the benefit of erlotinib for PC
Given these preliminary data we hypothesize that EGFR activation is a characteristic feature of keratinopathies Further we expect that oral low-dose erlotinib will improve the scaling and skin thickening of the spectrum of keratinopathies and be tolerated by most patients For those who experience pain particularly from plantar involvement we predict that erlotinib therapy will improve mobility and pain Finally we aim to find the mechanism by which erlotinib improves the phenotypes of the various keratinopathies to better understand these disorders and predict response We will look specifically at the impact on differentiation vs hyperproliferation and barrier function as well as the immune modulatory effects of the erlotinib using a multi-omics approach
Given these preliminary data we hypothesize that EGFR activation is a characteristic feature of keratinopathies Further we expect that oral low-dose erlotinib will improve the scaling and skin thickening of the spectrum of keratinopathies and be tolerated by most patients For those who experience pain particularly from plantar involvement we predict that erlotinib therapy will improve mobility and pain Finally we aim to find the mechanism by which erlotinib improves the phenotypes of the various keratinopathies to better understand these disorders and predict response We will look specifically at the impact on differentiation vs hyperproliferation and barrier function as well as the immune modulatory effects of the erlotinib using a multi-omics approach
Detailed Description:
We will conduct the first interventional multi-site Phase 12a 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 erlotinib8 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
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 erlotinib8 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None