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

April 11, 2013 updated by: Dartmouth-Hitchcock Medical Center

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center
    • Vermont
      • White River Junction, Vermont, United States, 05009
        • White River Junction VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Cancer diagnosis of Renal Cell Carcinoma (RCC) or Hepatocellular Carcinoma (HCC) or Colorectal Carcinoma

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dartmouth-Hitchcock Medical Center

Investigators

  • Principal Investigator: Alexey V Danilov, MD, Dartmouth-Hitchcock Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

April 1, 2013

Study Completion (Actual)

April 1, 2013

Study Registration Dates

First Submitted

October 31, 2011

First Submitted That Met QC Criteria

November 7, 2011

First Posted (Estimate)

November 8, 2011

Study Record Updates

Last Update Posted (Estimate)

April 15, 2013

Last Update Submitted That Met QC Criteria

April 11, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D11004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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