Preventing Squamous Cell Skin Cancer

NCT02347813 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: URochester RSRB 00052209
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Squamous Cell Carcinoma of the Skin

Keywords

squamous cell carcinoma; pioglitazone; PPARgamma; skin cancer

Outcome Measures

Primary Outcomes (1)

• Mean Number of Squamous Cell Carcinomas

  Squamous Cell Carcinomas were counted by visual inspection of the all skin on the body.

  1 year

Secondary Outcomes (1)

• Mean Number of Other Skin Cancers

  1 year

Study Arms (2)

Delayed Intervention

OTHER

After enrollment, subjects will be observed for 24 weeks for skin cancer tumors. Tumors will be appropriately treated as per standard of care. Then they will begin the pioglitazone regimen for 24 more weeks, during which time skin cancer tumors will be observed and appropriately treated as per standard of care.

Drug: Pioglitazone

Immediate Intervention

OTHER

Subjects will begin the 24 week pioglitazone regimen immediately after enrollment, during which time skin cancer tumors will be observed and appropriately treated as per standard of care. After 24 weeks of drug, subjects will be observed for 24 weeks for skin cancer tumors. Tumors will be appropriately treated as per standard of care.

Drug: Pioglitazone

Interventions

Pioglitazone DRUG

15 mg of pioglitazone orally for 2 weeks, and if well tolerated, 30 mg pioglitazone orally for 5 1/2 months.

Also known as: Actos

Delayed Intervention; Immediate Intervention

Eligibility Criteria

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

You may qualify if:

• \>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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Rochester: lead

Related Publications (1)

• Mantel A, Carpenter-Mendini A, VanBuskirk J, Pentland AP. Aldo-keto reductase 1C3 is overexpressed in skin squamous cell carcinoma (SCC) and affects SCC growth via prostaglandin metabolism. Exp Dermatol. 2014 Aug;23(8):573-8. doi: 10.1111/exd.12468. Epub 2014 Jul 16.

  PMID: 24917395 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Carotid Intimal Medial Thickness 1; Skin Neoplasms

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

This study was under enrolled and therefore was not powered to show a difference between the two arms.

Results Point of Contact

• Title: Alice Pentland, MD
• Organization: University of Rochester

alice_pentland@urmc.rochester.edu

585-275-1998

Study Officials

• Alice P. Pentland, M.D.

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 21, 2015
• First Posted: January 27, 2015
• Study Start: November 1, 2014
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2019
• Last Updated: June 23, 2020
• Results First Posted: June 23, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share