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Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer Prevention

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ClinicalTrials.gov Identifier: NCT04375813
Recruitment Status : Recruiting
First Posted : May 5, 2020
Last Update Posted : September 22, 2020
Sponsor:
Information provided by (Responsible Party):
Rapamycin Holdings Inc. ( 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.

Condition or disease Intervention/treatment Phase
Non-muscle Invasive Bladder Cancer Drug: eRapa Drug: Placebos Phase 2

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, 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 following enrollment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 166 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This 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 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 following enrollment.
Masking: Double (Participant, Investigator)
Masking Description: Once the list is generated, a non-study staff member will deliver the list to the designated pharmacist. The pharmacist will follow the generated list in consecutive order of enrollment to determine which group the subject will be assigned. The pharmacist will prepare the correct study drug (Placebo or eRapa (encapsulated rapamycin) 0.5 mg) and label the drug with subject information. Research staff will transport drug from pharmacy to clinic and provide for subject. Randomization will remain double blinded for study staff and subject. Patients will be given a once-daily oral eRapa (encapsulated rapamycin) at 0.5 mg or placebo MF for 1 year. Once the primary objectives have been met (i.e., all participants have completed follow up), the study staff and PI will be unblinded to the randomized study treatment arms. The above mentioned generated randomization list with subject assignments will be provided to the study staff and PI by the designated pharmacist.
Primary Purpose: Prevention
Official Title: Phase II Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer Prevention
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : August 2025
Estimated Study Completion Date : August 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Active Comparator: Active Study Drug Group
Patients will be given 0.5mg eRapa (encapuslated rapamycin) orally each weekday (Monday-Friday) for one year.
Drug: eRapa
0.5mg eRapa (encapsulated rapamycin) oral capsules
Other Name: encapsulated rapamycin

Placebo Comparator: Placebo Group
Patients will be given a placebo (visually identical to the eRapa (encapsulated rapamycin)) orally each weekday (Monday-Friday) for one year.
Drug: Placebos
placebo capsules visually identical to eRapa oral capsules




Primary Outcome Measures :
  1. Determine 1-year Recurrence Free Survival (RFS) rate [ Time Frame: 1 year ]
    The primary analysis will be the estimation of the RFS rate with the 95% confidence interval and comparison of the rate to the historical rate of 68% using the single arm log-rank test (one-sided alpha = 0.05). If the observed rate of RFS is 80% the expected number of events is about 20-28. Recurrence confirmed by pathologic examination of biopsied tissue.

  2. Change in Urinary Quality of Life [ Time Frame: Scored at baseline and months 9 and 21. ]
    Urinary Quality of Life measured using the urinary domain of the QLQ-BLS24 Index (a 24-item questionnaire that measures quality of life as it relates to urinary symptoms, sexual function, and bother domains). QLQ-BLS24 with a scale ranging from 24-96, and higher scores are worse.

  3. Change in Cognitive Function [ Time Frame: EXIT will be scored at baseline and on months 12, 24, 36, and 48. ]
    Cognitive function will be measured throughout the study period using EXIT. The EXIT is a brief 25-item interview that will be used by trained research staff to evaluate executive cognitive dysfunction of subjects.

  4. Change in Cognitive Function [ Time Frame: SLUMS will be scored at baseline and on months 12, 24, 36, and 48. ]
    Cognitive function will be measured throughout the study period using St. Louis University Mental Status exam (SLUMS). The SLUMS exam will be used to evaluate memory, digit span and animal fluency.

  5. Change in Cognitive Function [ Time Frame: TAPS will be scored at baseline and on months 3, 6, 12, and 24. ]
    Cognitive function will be measured throughout the study period using Texas Assessment of Processing Speed (TAPS). The TAPS test will evaluate digit/symbol coding.

  6. Change in cytoscopy consistent with recurrence (time to recurrence) [ 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. ]
    Change in cytoscopy results from baseline consistent with recurrence, confirmed by pathologic examination of biopsied tissue.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04375813


Contacts
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Contact: Lauren Zahra, MS 210-540-4695 lzahra@cancerinsight.com
Contact: Stephanie Althoff 210-722-4936 salthoff@cancerinsight.com

Locations
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United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Donna Mitchell    214-645-8789    donna.mitchell@utsouthwestern.edu   
Contact: Aphrihl Dennis    214-645-8791    aphrihl.dennis@utsouthwestern.edu   
Principal Investigator: Yair Lotan, MD         
UT Health San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Emily Rios    210-567-3224    RiosE3@uthscsa.edu   
Principal Investigator: Robert S Svatek, MD         
Sponsors and Collaborators
Rapamycin Holdings, Inc. dba Emtora Biosciences
Investigators
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Principal Investigator: Robert S Svatek, MD, MSCI UT Health San Antonio
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Responsible Party: Rapamycin Holdings, Inc. dba Emtora Biosciences
ClinicalTrials.gov Identifier: NCT04375813    
Other Study ID Numbers: ER-B01
First Posted: May 5, 2020    Key Record Dates
Last Update Posted: September 22, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs