A Study of Rapamycin Combined With Intravesical BCG in Patients With Non-muscle Invasive Bladder Cancer
Primary Purpose
Bladder Cancer
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sirolimus
Sponsored by
About this trial
This is an interventional treatment trial for Bladder Cancer focused on measuring BCG, Rapamycin
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
Sites / Locations
- University of Texas Health Science Center at San Antonio
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
No Intervention
Arm Label
Rapamycin 0.5mg
Rapamycin 2.0mg
Control
Arm Description
Subject will take Rapamycin (Sirolimus) 0.5mg once daily for approximately 28 days
Subject will take Rapamycin (Sirolimus) 2.0mg once daily for approximately 28 days
Subject will be apart of the control group and won't take the study drug being tested
Outcomes
Primary Outcome Measures
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
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
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
Secondary Outcome Measures
Full Information
NCT ID
NCT02753309
First Posted
April 18, 2016
Last Updated
March 17, 2021
Sponsor
The University of Texas Health Science Center at San Antonio
1. Study Identification
Unique Protocol Identification Number
NCT02753309
Brief Title
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
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
June 2016 (undefined)
Primary Completion Date
December 1, 2019 (Actual)
Study Completion Date
March 2, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Health Science Center at San Antonio
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
BCG, Rapamycin
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rapamycin 0.5mg
Arm Type
Active Comparator
Arm Description
Subject will take Rapamycin (Sirolimus) 0.5mg once daily for approximately 28 days
Arm Title
Rapamycin 2.0mg
Arm Type
Active Comparator
Arm Description
Subject will take Rapamycin (Sirolimus) 2.0mg once daily for approximately 28 days
Arm Title
Control
Arm Type
No Intervention
Arm Description
Subject will be apart of the control group and won't take the study drug being tested
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
Rapamycin, Rapamune
Primary Outcome Measure Information:
Title
Percentage change in systemic (whole blood) gamma-delta T cells frequency
Description
Change will be evaluated by comparing percentage increase or decrease following rapamycin or control (no therapy) against baseline measures
Time Frame
4 weeks and 3 months after therapy
Title
Percentage change in systemic (whole blood) gamma-delta T cell proliferation in response to BCG-specific antigens
Description
Change will be evaluated by comparing percentage increase or decrease following rapamycin or control (no therapy) against baseline measures
Time Frame
4 weeks and 3 months after therapy
Title
Percentage change in systemic (whole blood) Ag85 peptide-specific CD4 and CD8 T lymphocytes measured using human IFN-gamma release.
Description
Change will be evaluated by comparing percentage increase or decrease following rapamycin or control (no therapy) against baseline measures
Time Frame
4 weeks and 3 months after therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Svatek, MD
Organizational Affiliation
The University of Texas Health Science Center at San Antonio
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
33653802
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.
Results Reference
derived
Learn more about this trial
A Study of Rapamycin Combined With Intravesical BCG in Patients With Non-muscle Invasive Bladder Cancer
We'll reach out to this number within 24 hrs