Secondary Prevention Trial of Rapamycin in Patients With Resected Non-muscle Invasive Bladder Cancer

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).

Study Overview

• Status: Withdrawn
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Rapamycin

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo Oral Tablet; Subject will be randomized to take the Placebo once daily for 2 years or until disease recurrence	Drug: Placebo Oral Tablet; Subject will be randomized to one of the 2 arms
ACTIVE_COMPARATOR: Sirolimus (Rapamycin) 0.5 mg/day for 2 years; Subject will be randomized to take Sirolimus (Rapamycin) 0.5mg once daily for 2 years or until disease recurrence	Drug: Rapamycin; Subject will be randomized to one of the 2 arms; Other Names: Sirolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Test the hypothesis that rapamycin 0.5 mg daily increases recurrence-free survival for patients with non-muscle invasive bladder cancer	Recurrence is defined as histologically-proven bladder cancer (stage CIS, Ta, T1 or ≥T2)	Patients are treated for 2 years or until disease relapse

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Recurrence is defined as histologically-proven bladder cancer (stage CIS, Ta, T1 or ≥T2)	Patients are treated for 2 years or until disease relapse
To compare the effects of rapamycin on BCG-specific immunity during treatment of non-muscle invasive bladder cancer with maintenance BCG.	BCG antigen-specific IFN-gamma ELISPOT responses will be measured	baseline and 6 months after registration

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2018
• Primary Completion (ANTICIPATED): February 1, 2022
• Study Completion (ANTICIPATED): May 1, 2022

Study Registration Dates

• First Submitted: September 26, 2017
• First Submitted That Met QC Criteria: September 26, 2017
• First Posted (ACTUAL): October 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 12, 2019
• Last Update Submitted That Met QC Criteria: June 7, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: HSC20170277H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No