Effect of Sorafenib or Regorafenib on P63 Expression and Keratinocyte Differentiation in Human Skin

Hepatocellular Carcinoma Clinical Trial

Official title:

A Study of the Effect of Sorafenib or Regorafenib on p63 Expression and Keratinocyte Differentiation in Human Skin

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01466504
• Other study ID #: D11004
• Status: Terminated
• Phase: N/A
• First received: October 31, 2011
• Last updated: April 11, 2013
• Start date: May 2011
• Est. completion date: April 2013

Study information

• Verified date: March 2013
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Carcinoma, Renal Cell
• Colorectal Carcinoma
• Colorectal Neoplasms
• Hepatocellular Carcinoma
• Renal Cell Carcinoma

Intervention

Procedure:
• skin punch biopsy
Skin biopsy prior to sorafenib or regorafenib treatment and when rash appears or 12 weeks into treatment.

Locations

Country	Name	City	State
United States	Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	White River Junction VA Medical Center	White River Junction	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	p63 expression levels	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.	Week 12	No
Secondary	Tumor response	Sorafenib and regorafenib potentially interfere with p63 expression and keratinocyte differentiation and skin remodeling. The extent of interference may indicate extent of tumor response.	Week 12	No

External Links

•   Norris Cotton Cancer Center