No funding was received, no subjects were enrolled

The study is a multi-site Phase 3 double-blinded randomized placebo-controlled trial. Subjects are randomly assigned to receive either a placebo or oral Sirolimus: 0.5 mg daily. All subjects will be treated for 2 years or until disease recurrence. Patients will undergo endoscopic evaluation of the bladder every 3 months for the first 2 years following enrollment and then every 6 months for an additional 2 years on study. Selection of BCG immune therapy is at the discretion of the treating urologist but in general is reserved for high-risk patients. Patients concurrently receiving BCG immune therapy will receive standard BCG therapy including induction (weekly for 6 weeks) and maintenance (weekly for 3 weeks at 3 months, 6 months, and then every 6 months following tumor resection).

Inclusion Criteria:

• Pathologically (histologically) proven diagnosis of non-muscle invasive (Ta, Tis or T1) bladder cancer within 60 days prior to enrollment
• 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)

Double-blinded for study staff (investigator) and patient