Preventing Squamous Cell Skin Cancer
Condition: Squamous Cell Carcinoma of the Skin
MeSH terms: Carcinoma, Squamous Cell
Intervention: Pioglitazone
Intervention description: 15 mg of pioglitazone orally for 2 weeks, and if well tolerated, 30 mg pioglitazone orally for 5 1/2 months.
Intervention MeSH terms: Pioglitazone
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: squamous cell carcinoma; pioglitazone; PPARgamma; skin cancer

Summary:

      This study is proposed based on our work showing that the diabetes drug Pioglitazone strongly
      inhibits growth of tissue cultured squamous cell carcinoma (SCC) of the skin. This occurs at
      concentrations readily achievable by oral administration of this drug using doses currently
      approved for the treatment of diabetes. In our study, we propose to enroll 40 non-diabetic
      adult subjects (18-80 yrs of age inclusive) with a documented clinical history of frequent
      occurrence of skin squamous cell cancer to receive Pioglitazone (Actos®,Takeda
      Pharmaceuticals). Each subject will receive usual care for all new tumors they develop while
      on study (i.e, excision and plastic repair). The study protocol will randomize (1:1) patients
      for 6 months of observation followed by 6 months of treatment (group 1) or 6 months of
      treatment with drug followed by observation for 6 months (to examine washout effects). The
      biopsy specimens collected on and off therapy will be examined to determine if they express
      AKR1C3, an enzyme we believe increases resistance of SCC to prostaglandin inflammatory
      mediators. We will also examine the histologic grade of the removed tumors and study whether
      Pioglitazone treatment can decrease the number of aggressive versus well differentiated
      tumors in study patients. This pilot study is designed to detect a statistically significant
      change in SCC tumor numbers but is not sponsored by the drug manufacturer. The data obtained
      will not be used to effect a change in the product label.
    

Eligibility criteria:

        Inclusion Criteria:

          -  >18 years of age, male or female, state of health stable

          -  Able understand protocol and give consent

          -  Has had treatment of 2 - 6 squamous cell carcinomas of the skin during the year prior
             to enrollment, & pathology is available for verification

          -  Stable treatment regimen for their skin cancer problems in place for 1 year, with
             expectation to keep medications the same during study

          -  Able to keep study appointments & comply with protocol

        Exclusion Criteria:

          -  Unwillingness or unable to complete informed consent process

          -  < 18 years of age

          -  Allergy to Pioglitazone

          -  Taking Rifampin, Trimethoprim, Celebrex or Gemfibrozil

          -  Pregnant or breastfeeding (Pregnancy Category C)

          -  History of heart failure NYHA Class III or Class IV

          -  Subjects with type 1 or type 2 diabetes

          -  Problems with pedal edema

          -  Liver disease (ETOH, viral hepatitis, drug-induced hepatitis) or elevated ALT, AST or
             total bilirubin

          -  Osteoporosis with high risk of fracture

          -  History of bladder cancer

          -  Recent change in chronic oral medications. Participants enrolled while on a systemic
             medication for their skin cancer must remain on treatment.