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

This study has been 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.)
Sponsor:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT01466504
First received: October 31, 2011
Last updated: April 11, 2013
Last verified: March 2013
  Purpose

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 Intervention
Renal Cell Carcinoma
Hepatocellular Carcinoma
Colorectal Carcinoma
Procedure: skin punch biopsy

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • p63 expression levels [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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:
  • Tumor response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.


Enrollment: 4
Study Start Date: May 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: skin punch biopsy
    Skin biopsy prior to sorafenib or regorafenib treatment and when rash appears or 12 weeks into treatment.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01466504

Locations
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
Investigators
Principal Investigator: Alexey V Danilov, MD Dartmouth-Hitchcock Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT01466504     History of Changes
Other Study ID Numbers: D11004
Study First Received: October 31, 2011
Last Updated: April 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
P63
Sorafenib
Regorafenib
rash
skin toxicity
RCC
HCC
colorectal carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Colorectal Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Liver Neoplasms
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014