Effect of Sorafenib or Regorafenib on P63 Expression and Keratinocyte Differentiation in Human Skin
| Status: | Completed |
|---|---|
| Conditions: | Colorectal Cancer, Liver Cancer, Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/30/2013 |
| Start Date: | May 2011 |
| End Date: | December 2013 |
| Contact: | Alexey V Danilov, MD |
| Email: | cancer.research.nurse@Dartmouth.edu |
| Phone: | 800-639-6918 |
A Study of the Effect of Sorafenib or Regorafenib on p63 Expression and Keratinocyte Differentiation in Human Skin
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.
Inclusion Criteria:
1. Male or female, 18 years old or older.
2. Histologically or cytologically confirmed diagnosis of a solid tumor (RCC, HCC, or
colorectal cancer).
3. Participants are planning to initiate treatment with either sorafenib or regorafenib
as a single chemotherapeutic agent
4. Able to swallow and retain oral medication and does not have any clinically relevant,
active gastrointestinal disease or other condition that may significantly alter
absorption, distribution, metabolism, or excretion of drugs.
5. Be able to provide written informed consent.
Exclusion Criteria
1. Patients who are or will be receiving other chemotherapeutic or molecularly targeted
agents in addition to sorafenib or regorafenib
2. Concurrent moderate or severe chronic inflammatory skin condition (eczema, psoriasis)
3. Concurrent blistering skin disorder of any severity (such as pemphigus, bullous
pemphigoid)
4. Connective tissue disorders with skin involvement (systemic lupus erythematosus,
scleroderma, dermatomyositis, etc.)
5. Patients manifesting an allergic skin reaction (such as urticaria) or skin reaction
as a complication of prior chemotherapy
6. Patients with skin lesions of infectious or non-infectious cause, precluding skin
biopsy
7. Patients not willing to undergo skin biopsy
8. Patients who are pregnant or planning to become pregnant during their participation
in the study.
9. Chemotherapy, targeted therapy, or biological therapy within two weeks of start of
treatment.
10. Ability to give informed consent is compromised by cognitive and/or decisional
impairment.
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