Sirolimus in Kidney Transplant Patients With Squamous Cell Skin Carcinoma

Phase 2

Terminated

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Sirolimus treatment	Sirolimus	Patients will receive sirolimus 5 weeks prior to removal of squamous cell skin carcinoma. After the 5 weeks of treatment, nephrology will determine/manage each patient's immunosuppressant therapy.

Primary Outcome Measures

Name	Time	Method
Measure of Squamous Cell Skin Carcinoma in Patients	Baseline, time of surgical removal (5 weeks) and 1 year.	Baseline: Measuring of squamous cell skin carcinoma, Week 5: Measuring and surgical removal of squamous cell skin cancer with microscopic evaluation, and in 1 year.

Secondary Outcome Measures

Name	Time	Method
Evaluation of Skin Tumor for Squamous Cell Skin Carcinoma	At baseline and time of surgical removal (5 weeks).	Tumor will be analyzed at baseline and time of surgical removal by both laboratory and microscopic testing.