Effect of Sorafenib or Regorafenib on P63 Expression and Keratinocyte Differentiation in Human Skin
|ClinicalTrials.gov Identifier: NCT01466504|
Recruitment Status : Terminated (Accrual did not meet expectations. Over nearly 2 years just 4 subjects were treated on study. The goal of 30 subjects was not attainable.)
First Posted : November 8, 2011
Last Update Posted : April 15, 2013
Skin toxicity is a frequently observed side effect in the era of "molecularly targeted therapies". Skin toxicity following administration of protein kinase inhibitors such as sorafenib, regorafenib, lapatinib, sunitinib, and others can be debilitating to the patient, resulting in dose reduction and discontinuation of treatment. The mechanisms of skin toxicity induced by targeted chemotherapy, such as sorafenib or regorafenib, are poorly understood. Further research is warranted to better understand the pathophysiology of drug-related skin toxicity in this setting and develop correction strategies. This study tests the hypothesis that sorafenib and regorafenib interfere with p63 expression and keratinocyte differentiation and skin remodeling.
Eligible study participants will be evaluated clinically for evidence of skin toxicity during their visits to the outpatient Oncology clinics. Study participants will undergo skin biopsies before sorafenib or regorafenib treatment is initiated and once rash develops or 12 weeks into treatment with sorafenib or regorafenib. Skin biopsies will be performed in Oncology clinics by the study investigators and clinic support staff.
Study participants will undergo both skin biopsies regardless of whether they develop a rash. In patients who develop a rash the most representative lesion will be biopsied. A normal appearing area of skin will be biopsied in participants who do not develop a rash.
|Condition or disease||Intervention/treatment|
|Renal Cell Carcinoma Hepatocellular Carcinoma Colorectal Carcinoma||Procedure: skin punch biopsy|
|Study Type :||Observational|
|Actual Enrollment :||4 participants|
|Official Title:||A Study of the Effect of Sorafenib or Regorafenib on p63 Expression and Keratinocyte Differentiation in Human Skin|
|Study Start Date :||May 2011|
|Primary Completion Date :||April 2013|
|Study Completion Date :||April 2013|
Procedure: skin punch biopsy
- p63 expression levels [ Time Frame: Week 12 ]Tissue collection is done within 7 days prior to treatment and when rash develops. If no rash develops, normal skin will be biopsied at week twelve of treatment.
- Tumor response [ Time Frame: Week 12 ]Sorafenib and regorafenib potentially interfere with p63 expression and keratinocyte differentiation and skin remodeling. The extent of interference may indicate extent of tumor response.
Biospecimen Retention: Samples Without DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01466504
|United States, New Hampshire|
|Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center|
|Lebanon, New Hampshire, United States, 03756|
|United States, Vermont|
|White River Junction VA Medical Center|
|White River Junction, Vermont, United States, 05009|
|Principal Investigator:||Alexey V Danilov, MD||Dartmouth-Hitchcock Medical Center|