Clinical trial NCT01466504: Effect of Sorafenib or Regorafenib on P63 Expression and Keratinocyte Differentiation in Human Skin
Official title: A Study of the Effect of Sorafenib or Regorafenib on p63 Expression and Keratinocyte Differentiation in Human Skin
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Renal Cell Carcinoma
Hepatocellular Carcinoma
Colorectal Carcinoma
Keywords: P63
Sorafenib
Regorafenib
rash
skin toxicity
RCC
HCC
colorectal carcinoma
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2011-11-08
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cancer diagnosis of Renal Cell Carcinoma (RCC) or Hepatocellular Carcinoma (HCC) or Colorectal Carcinoma

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: p63 expression levels
timeFrame: Week 12
Secondary outcomes:
measure: Tumor response
timeFrame: Week 12
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center
state: New Hampshire
city: White River Junction
country: United States
facility: White River Junction VA Medical Center
state: Vermont
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Alexey V Danilov, MD
role: PRINCIPAL_INVESTIGATOR
References: