Bladder Cancer
Conditions
Brief summary
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).
Interventions
DRUGRapamycin
Subject will be randomized to one of the 2 arms
DRUGPlacebo Oral Tablet
Subject will be randomized to one of the 2 arms
Sponsors
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blinded for study staff (investigator) and patient
Intervention model description
When it is determined that you are eligible for the study, you will be assigned by chance (like flipping a coin) to one of 2 study groups. * Sirolimus 0.5 mg/day for 2 years or until disease recurrence * Placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Test the hypothesis that rapamycin 0.5 mg daily increases recurrence-free survival for patients with non-muscle invasive bladder cancer | Patients are treated for 2 years or until disease relapse | Recurrence is defined as histologically-proven bladder cancer (stage CIS, Ta, T1 or ≥T2) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To determine effects of rapamycin on recurrence-free survival (RFS) for subgroup of patients with non-muscle invasive bladder cancer concurrently receiving BCG immune therapy. | Patients are treated for 2 years or until disease relapse | Recurrence is defined as histologically-proven bladder cancer (stage CIS, Ta, T1 or ≥T2) |
| To compare the effects of rapamycin on BCG-specific immunity during treatment of non-muscle invasive bladder cancer with maintenance BCG. | baseline and 6 months after registration | BCG antigen-specific IFN-gamma ELISPOT responses will be measured |
Countries
United States
Outcome results
None listed