eRapa (encapsulated rapamycin) will be investigated for secondary prevention in patients with diagnosed non-muscle invasive bladder cancer (NMIBC) through a phase II double-blind randomized controlled trial of long-term (one year) prevention with eRapa versus placebo. The primary hypothesis is that eRapa decreases the risk of cancer relapse for patients with NMIBC. Secondary hypotheses are that eRapa can improve certain immune parameters and improve cognition and physical function without adversely affecting patient-reported outcomes and quality of life.
The study is a multi-site phase II double-blind randomized trial. Subjects will be randomized
into placebo arm or intervention arm with low dose (0.5 mg) eRapa (encapsulated rapamycin)
Monday-Friday for one year or until disease recurrence. Patients will undergo endoscopic
evaluation of the bladder every 3 months for 2 years, then every 6 months for 2 years, then
annually following registration. Some patients may also concurrently receive BCG immune
therapy maintenance (weekly for 6 weeks for induction period, weekly for 3 weeks at 3 months,
6 months, and then every 6 months for a total of 7 maintenance cycles following tumor
removal) per standard of care. Patient-reported outcome (PRO) assessments, cognitive
assessments, and physical assessments will be completed according to the study calendar.
Research blood to assess safety, immune response and rapamycin level will be collected
regularly throughout the study period. Participants will be followed for up to 4 years
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||November 2020||Phase 2||Interventional|
Primary Outcome 1 - Measure: Determine 1-year Recurrence Free Survival (RFS) rate
Primary Outcome 1 - Time Frame: 1 year
Primary Outcome 2 - Measure: Change in Urinary Quality of Life
Primary Outcome 2 - Time Frame: Scored at baseline and months 9 and 21.
Primary Outcome 3 - Measure: Change in Cognitive Function
Primary Outcome 3 - Time Frame: EXIT will be scored at baseline and on months 12, 24, 36, and 48.
Primary Outcome 4 - Measure: Change in Cognitive Function
Primary Outcome 4 - Time Frame: SLUMS will be scored at baseline and on months 12, 24, 36, and 48.
Primary Outcome 5 - Measure: Change in Cognitive Function
Primary Outcome 5 - Time Frame: TAPS will be scored at baseline and on months 3, 6, 12, and 24.
Primary Outcome 6 - Measure: Change in cytoscopy consistent with recurrence (time to recurrence)
Primary Outcome 6 - Time Frame: Patients will undergo office-based cystoscopy with urine cytology every 3 months for the first 2 years, then every 6 months for 2 years, then annually until 4 years after the last patient is enrolled, with biopsies per standard of care if necessary.
- Pathologically (histologically) proven diagnosis of non-muscle invasive (Ta, Tis, or
T1) bladder cancer within 90 days prior to enrollment
- Able to give informed consent
- 18 years or older
- Patients must not be taking oral glucocorticoids at the time of registration
- Not have active, uncontrolled infections
- No other prior non-bladder malignancy is allowed except for the following: adequately
treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately
treated Stage I or II cancer from which the patient is currently in complete
remission, or any other cancer from which the patient has been disease free for five
- Patients with localized prostate cancer who are being followed by an active
survelillance program are also eligible.
- Patients must not be pregnant or nursing, as the use of Intravesical BCG is not
recommended during pregnancy. Women/ men of reproductive potential must have agreed to
use an effective contraceptive method. A woman is considered to be of reproductive
potential" if she has had menses at any time in the preceding 12 consecutive months.
In addition to routine contraceptive methods, "effective contraception" also includes
heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect
of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, or
bilateral tubal ligation. However, if at any point a previously celibate patient
chooses to become heterosexually active during the time period for use of
contraceptive measures outlined in the protocol, he/she is responsible for beginning
contraceptive measures. Both male and female patients will be required to disclose
contraception method during screening and agree to continue to use that contraception
method through the end of their participation in the study.
- Patients must have had all grossly visible papillary tumors removed within 90 days
prior to registration or cystoscopy confirming no grossly visible papillary tumors
within 90 days prior to registration.
- Patients with T1 disease must have cross-sectional imaging of abdomen/pelvis
demonstrating no evidence of nodal involvement or metastatic disease (MRI or CT scan)
within 90 days prior to registration. Patients with T1 disease must have re-resection
confirming ≤ T1 disease within 90 days prior to registration.
- Patients must no have received prior intravesical BCG
- Have muscle-invasive or higher (≥T2) bladder cancer
- Unable to give informed consent
- Age 17 or younger
- Taking oral glucocorticoids at the time of registration
- Another cancer requiring active treatment (except basal cell carcinoma or squamous
cell carcinoma of the skin)
- Patients at risk of pregnancy that are unwilling or unable to take effective
contraception during the study period, or patients that are nursing during the study
period. Women/ Men of reproductive potential must have agreed to use an effective
contraceptive method or will be considered ineligible for study participation.
- Evidence of nodal involvement or metastatic disease (MRI or CT scan) within 90 days
prior to registration
- History of prior intravesical BCG
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Robert S Svatek, MD, MSCI
Role: Principal Investigator
Affiliation: UT Health San Antonio
Name: Stephanie Althoff
|UT Southwestern Medical Center
Dallas, Texas 75390
|UT Health San Antonio
San Antonio, Texas 78229