A Study of Rapamycin Combined With Intravesical BCG in Patients With Non-muscle Invasive Bladder Cancer

Study Overview
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Brief Summary
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This study is looking at the effects of Sirolimus (Rapamycin) on BCG-specific immunity during treatment of non-muscle invasive bladder cancer (NMIBC) with maintenance BCG.

Detailed Description
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This study will evaluate change from baseline in gamma-delta T cell numbers and function and Ag85 peptide-specific T cell responses following treatment.

Official Title
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A Randomized Study of Rapamycin Combined With Intravesical BCG in Patients With Non-muscle Invasive Bladder Cancer

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: Sirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically (histologically) proven diagnosis of non-muscle invasive (Ta, Tis or T1) bladder cancer In their treating physician's opinion is a good candidate for BCG therapy Be able to give informed consent Be age 18 or older Not be in an immunosuppressed state (e.g. HIV, use of chronic steroids) Not have active, uncontrolled infections Not be on agents known to alter rapamycin metabolism significantly Not have a reported history of liver disease (e.g. cirrhosis) Not have a prior history of non-bladder cancer unless the cancer is clinically stable and not requiring active treatment except basal cell carcinoma or squamous cell carcinoma of the skin. Not pregnant, or taking effective contraception before rapamycin therapy, during therapy and for 12 weeks after discontinuation of therapy. Exclusion Criteria: Have muscle-invasive (≥T2) bladder cancer Unable to give informed consent Age < 18 Immunosuppressed state (e.g. HIV, use of chronic steroids) Active, uncontrolled infections On agents known to alter rapamycin metabolism significantly Another cancer requiring active treatment (except basal cell carcinoma or squamous cell carcinoma of the skin) Patients at risk of pregnancy who are unwilling or unable to take effective contraception before rapamycin therapy, during therapy, and for 12 weeks after discontinuation of therapy. Individuals with a reported history of liver disease (e.g. cirrhosis) Individuals who are not a good candidate for BCG in their treating physician's opinion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rapamycin 0.5mg<br>Subject will take Rapamycin (Sirolimus) 0.5mg once daily for approximately 28 days | Drug: Sirolimus<br> <br> * Other names: Rapamune;|
| Active Comparator: Rapamycin 2.0mg<br>Subject will take Rapamycin (Sirolimus) 2.0mg once daily for approximately 28 days | Drug: Sirolimus<br> <br> * Other names: Rapamune;|
| No Intervention: Control<br>Subject will be apart of the control group and won't take the study drug being tested | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in systemic (whole blood) gamma-delta T cells frequency | Change will be evaluated by comparing percentage increase or decrease following rapamycin or control (no therapy) against baseline measures | 4 weeks and 3 months after therapy | 
| Percentage change in systemic (whole blood) gamma-delta T cell proliferation in response to BCG-specific antigens | Change will be evaluated by comparing percentage increase or decrease following rapamycin or control (no therapy) against baseline measures | 4 weeks and 3 months after therapy | 
| Percentage change in systemic (whole blood) Ag85 peptide-specific CD4 and CD8 T lymphocytes measured using human IFN-gamma release. | Change will be evaluated by comparing percentage increase or decrease following rapamycin or control (no therapy) against baseline measures | 4 weeks and 3 months after therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCG, Rapamycin