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

NCT01466504 | Terminated DMC

• 1 other identifier: D11004
• Study Type: observational
• Target: 4
• Locations: 1 country
• Sites: 2

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.

Conditions

Renal Cell Carcinoma; Hepatocellular Carcinoma; Colorectal Carcinoma

Keywords

P63; Sorafenib; Regorafenib; rash; skin toxicity; RCC; HCC; colorectal carcinoma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Tumor response

  Week 12

Interventions

skin punch biopsy PROCEDURE

Skin biopsy prior to sorafenib or regorafenib treatment and when rash appears or 12 weeks into treatment.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• Male or female, 18 years old or older.
• Histologically or cytologically confirmed diagnosis of a solid tumor (RCC, HCC, or colorectal cancer).
• Participants are planning to initiate treatment with either sorafenib or regorafenib as a single chemotherapeutic agent
• 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.
• Be able to provide written informed consent.

You may not qualify if:

• Patients who are or will be receiving other chemotherapeutic or molecularly targeted agents in addition to sorafenib or regorafenib
• Concurrent moderate or severe chronic inflammatory skin condition (eczema, psoriasis)
• Concurrent blistering skin disorder of any severity (such as pemphigus, bullous pemphigoid)
• Connective tissue disorders with skin involvement (systemic lupus erythematosus, scleroderma, dermatomyositis, etc.)
• Patients manifesting an allergic skin reaction (such as urticaria) or skin reaction as a complication of prior chemotherapy
• Patients with skin lesions of infectious or non-infectious cause, precluding skin biopsy
• Patients not willing to undergo skin biopsy
• Patients who are pregnant or planning to become pregnant during their participation in the study.
• Chemotherapy, targeted therapy, or biological therapy within two weeks of start of treatment.
• Ability to give informed consent is compromised by cognitive and/or decisional impairment.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (2)

Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

White River Junction VA Medical Center

White River Junction, Vermont, 05009, United States

Location

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.

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma, Hepatocellular; Colorectal Neoplasms; Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip-Palate Syndrome 3; Exanthema

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Alexey V Danilov, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2011
• First Posted: November 8, 2011
• Study Start: May 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: April 15, 2013

Record last verified: 2013-03

Locations

US (2)