Clinical trial NCT02753309: A Study of Rapamycin Combined With Intravesical BCG in Patients With Non-muscle Invasive Bladder Cancer
Official title: A Randomized Study of Rapamycin Combined With Intravesical BCG in Patients With Non-muscle Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Bladder Cancer
Keywords: BCG
Rapamycin
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2016-04-27
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Percentage change in systemic (whole blood) gamma-delta T cells frequency
timeFrame: 4 weeks and 3 months after therapy
measure: Percentage change in systemic (whole blood) gamma-delta T cell proliferation in response to BCG-specific antigens
timeFrame: 4 weeks and 3 months after therapy
measure: Percentage change in systemic (whole blood) Ag85 peptide-specific CD4 and CD8 T lymphocytes measured using human IFN-gamma release.
timeFrame: 4 weeks and 3 months after therapy
Secondary outcomes:
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Robert Svatek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ji N, Mukherjee N, Reyes RM, Gelfond J, Javors M, Meeks JJ, McConkey DJ, Shu ZJ, Ramamurthy C, Dennett R, Curiel TJ, Svatek RS. Rapamycin enhances BCG-specific gammadelta T cells during intravesical BCG therapy for non-muscle invasive bladder cancer: a randomized, double-blind study. J Immunother Cancer. 2021 Mar;9(3):e001941. doi: 10.1136/jitc-2020-001941.