Sirolimus in Kidney Transplant Patients With Squamous Cell Skin Carcinoma

A Phase II Study of Sirolimus in Renal Transplant Patients Diagnosed With New or Recurrent Squamous Cell Skin Carcinoma Currently on Calcineurin-based Immunosuppression.

Solid organ transplant recipients (SOTR) have a 3-5x increased occurrence of cancer in contrast to the general population with basal and squamous cell skin cancer. The use of immunosuppressant or anti-rejection drugs that are needed after SOTR is known to increase the risk of developing certain kinds of cancer. The purpose of this study is to find out how well Sirolimus (also known as Rapamune) works at treating squamous cell carcinoma in renal transplant patients.

This is a Phase II randomized study to evaluate the effectiveness of Sirolimus in treating and preventing squamous cell skin cancer carcinoma using a Simon's 2-stage design. As part of the study, after the biopsy results of the skin cancer show squamous cell carcinoma and consent had been obtain, the participant will begin taking Sirolimus. The calcineurin inhibitor (tacrolimus or cyclosporine) will be discontinued once the transplant doctors find that the participants Sirolimus is therapeutic by checking blood tests once a week x 3 weeks. Approximately 5 weeks after starting Sirolimus, the squamous cell skin cancer will be removed by a surgeon. Participant next follow up visit for the study is scheduled one year post-operatively. .The study will look at your squamous cell skin cancer under the microscope to see if sirolimus had any effect at treating your squamous cell skin cancer.

Inclusion Criteria:

• Histologically or cytologically proven squamous cell skin carcinoma
• Recipient of a renal organ transplant at least one year prior to study enrollment
• Receiving a CNI for at least 6 months prior to diagnosis of skin cancer
• No current evidence of graft rejection, except low-grade, chronic graft rejection
• Measurable disease by caliper measurement
• Life expectancy > 6 months
• Age of at least 18 years
• Adequate organ and marrow function as determined by ANC, HGB, PLT, Total Bili, AST, and creatinine clearance
• Ability to understand/willingness to sign a written informed consent form

Exclusion Criteria:

• Inability to give informed consent
• Major surgery within 4 week prior to starting study drug
• Chronic or non-healing open wounds
• Pregnant and nursing women
• Women and men of child-bearing potential must agree to use adequate contraception prior to study entry and for the study duration
• Prior use of an mTOR inhibitor
• Pre-existing clinically significant cardiac, hepatic, pulmonary, or renal dysfunction
• HIV-positive patients
• Proteinuria (> 1 gram)
• Prior or current history of uncontrolled hyperlipidemia (cholesterol > 302 mg/dl or triglycerides 354 mg/dl
• Currently receiving any investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sirolimus (mTOR inhibitors)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrythmia, or psychiatric illness/social situations that would limit compliance with study requirements