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

NCT02753309 | Completed Early Phase 1 DMC

• 1 other identifier: HSC20160162H
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Bladder Cancer

Keywords

BCG; Rapamycin

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (3)

Rapamycin 0.5mg

ACTIVE COMPARATOR

Subject will take Rapamycin (Sirolimus) 0.5mg once daily for approximately 28 days

Drug: Sirolimus

Rapamycin 2.0mg

ACTIVE COMPARATOR

Subject will take Rapamycin (Sirolimus) 2.0mg once daily for approximately 28 days

Drug: Sirolimus

Control

NO INTERVENTION

Subject will be apart of the control group and won't take the study drug being tested

Interventions

Sirolimus DRUG

Also known as: Rapamycin, Rapamune

Rapamycin 0.5mg; Rapamycin 2.0mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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.

  PMID: 33653802 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Robert Svatek, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2016
• First Posted: April 27, 2016
• Study Start: June 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: March 2, 2021
• Last Updated: March 19, 2021

Record last verified: 2021-03

Locations

US (1)