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Brief Title: Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer Prevention

Phase II Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer Prevention

INTRODUCTION

  • Org Study ID: ER-B01
  • Secondary ID: R01CA252057
  • NTC ID: NCT04375813
  • Sponsor: Rapamycin Holdings, Inc. dba Emtora Biosciences

BRIEF SUMMARY

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.

DETAILED DESCRIPTION

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, and at year 5. 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 5 years following enrollment.

  • Overall Status
    Recruiting
  • Start Date
    January 25, 2021
  • Phase
    Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Determine 1-year Recurrence Free Survival (RFS) rate

Primary Outcome 1 - Timeframe: 1 year

Primary Outcome 2 - Measure: Change in Urinary Quality of Life

Primary Outcome 2 - Timeframe: Scored at baseline and months 3, 6, 12 and 24. For any subject who has a recurrence after enrollment, but prior to completing a full year of dosing at Visit 6, this will also be measured at the End of Treatment visit.

Primary Outcome 3 - Measure: Change in Cognitive Function

Primary Outcome 3 - Timeframe: EXIT will be scored at baseline and on months 12 and 24.For any subject who has a recurrence after enrollment, but prior to completing a full year of dosing at Visit 6, this will also be measured at the End of Treatment visit.

Primary Outcome 4 - Measure: Change in Cognitive Function

Primary Outcome 4 - Timeframe: SLUMS will be scored at baseline and on months 12 and 24.For any subject who has a recurrence after enrollment, but prior to completing a full year of dosing at Visit 6, this will also be measured at the End of Treatment visit.

Primary Outcome 5 - Measure: Change in Cognitive Function

Primary Outcome 5 - Timeframe: TAPS will be scored at baseline and on months 6, 12, and 24. For any subject who has a recurrence after enrollment, but prior to completing a full year of dosing at Visit 6, this will also be measured at the End of Treatment visit.

Primary Outcome 6 - Measure: Change in cytoscopy consistent with recurrence (time to recurrence)

Primary Outcome 6 - Timeframe: Patients will undergo office-based cystoscopy with urine cytology every 3 months for the first 2 years, then every 6 months for 2 years, and at year 5, with biopsies per standard of care if necessary.

Primary Outcome 7 - Measure: Change in Short Physical Performance Battery

Primary Outcome 7 - Timeframe: SPPB will be scored at baseline and on months 6, 12, and 24. For any subject who has a recurrence after enrollment, but prior to completing a full year of dosing at Visit 6, this will also be measured at the End of Treatment visit.

Primary Outcome 8 - Measure: Change in Handgrip Strength

Primary Outcome 8 - Timeframe: Handgrip Strength will be scored at baseline and on months 6, 12, and 24. For any subject who has a recurrence after enrollment, but prior to completing a full year of dosing at Visit 6, this will also be measured at the End of Treatment visit.

CONDITION

  • Non-muscle Invasive Bladder Cancer

ELIGIBILITY

Inclusion Criteria:
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 years.

- 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. Examples of effective contraception include hormonal contraception, double barrier method (condom with spermicidal cream, diaphragms with spermicidal cream, or condoms with diaphragms), Intrauterine device, and/or partner vasectomy. 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
Exclusion Criteria:
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

- History of prior Rapamycin treatment

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Robert S Svatek, MD, MSCI

Role: Principal Investigator

Affiliation: UT Health San Antonio

Overall Contact

Name: Robert S Svatek, MD, MSCI

Phone: 267-689-5835, 301-996-2249

Email: gstrauss@cancerinsight.com, mcorrell@cancerinsight.com

LOCATION

Facility Status Contact
Facility: UT Southwestern Medical Center
Dallas, Texas 75390
United States
Status: Recruiting Contact: Contact
Donna Mitchell
214-645-8789
donna.mitchell@utsouthwestern.edu
Facility: UT Health San Antonio
San Antonio, Texas 78229
United States
Status: Recruiting Contact: Principal Investigator
Yair Lotan, MD
210-567-1172
wheelera2@uthscsa.edu