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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. 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
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center

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.

Condition or disease Intervention/treatment
Renal Cell Carcinoma Hepatocellular Carcinoma Colorectal Carcinoma Procedure: skin punch biopsy

Study Type : Observational
Actual Enrollment : 4 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy
U.S. FDA Resources

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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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
skin biopsies will be performed using a 4mm biopsy punch. Participants will undero 2 skin biopsies - one prior to starting sorafenib or regorafenib, the other once rash develops. If a rash does not develop within 84 days a biopsy of normal skin will be done.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Cancer diagnosis of Renal Cell Carcinoma (RCC) or Hepatocellular Carcinoma (HCC) or Colorectal Carcinoma

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its 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
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Principal Investigator: Alexey V Danilov, MD Dartmouth-Hitchcock Medical Center

Additional Information:
Responsible Party: Dartmouth-Hitchcock Medical Center Identifier: NCT01466504     History of Changes
Other Study ID Numbers: D11004
First Posted: November 8, 2011    Key Record Dates
Last Update Posted: April 15, 2013
Last Verified: March 2013

Keywords provided by Dartmouth-Hitchcock Medical Center:
skin toxicity
colorectal carcinoma

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma, Renal Cell
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action