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Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer Prevention

Primary Purpose

Non-muscle Invasive Bladder Cancer

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

eRapa

Placebos

About this trial

This is an interventional prevention trial for Non-muscle Invasive Bladder Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

UT Southwestern Medical CenterRecruiting
South Texas Veterans Health Care System (recruiting for treatment at UT Health San Antonio)Recruiting
UT Health San AntonioRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active Study Drug Group

Placebo Group

Arm Description

Patients will be given 0.5mg eRapa (encapuslated rapamycin) orally each weekday (Monday-Friday) for one year.

Patients will be given a placebo (visually identical to the eRapa (encapsulated rapamycin)) orally each weekday (Monday-Friday) for one year.

Outcomes

Primary Outcome Measures

Determine 1-year Recurrence Free Survival (RFS) rate

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.

Change in Urinary Quality of Life

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.

Change in Cognitive Function

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.

Change in Cognitive Function

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.

Change in Cognitive Function

Cognitive function will be measured throughout the study period using Texas Assessment of Processing Speed (TAPS). The TAPS test will evaluate digit/symbol coding.

Change in cytoscopy consistent with recurrence (time to recurrence)

Change in cytoscopy results from baseline consistent with recurrence, confirmed by pathologic examination of biopsied tissue.

Change in Short Physical Performance Battery

The Short Physical Performance Battery (SPPB) consists of a balance test looking at the ability to maintain three standing positions for 10 seconds, a timed 4-meter walk in which subjects perform their walk at their preferred walking speed, and a chair stand test that times the ability of the subject to arise from a chair 5 times without using their arms. Each section is scored out of 4 points, for a total possible score of 12 points. This test provides information on several motor domains such as static and dynamic balance, coordination, and strength of lower limbs. Lower scores may be associated with increased disability risk. The SPPB and Handgrip Strength are physical assessments.

Change in Handgrip Strength

When measuring handgrip strength, the subject will be seated in a chair with the forearm at a 90-degree elbow bend. Three consecutive grip strengths will be completed with a standard grip strength dynamometer for both hands. The Handgrip Strength and SPPB are physical assessments.

Secondary Outcome Measures

Full Information

NCT ID

NCT04375813

First Posted

April 28, 2020

Last Updated

September 14, 2022

Sponsor

Rapamycin Holdings, Inc. dba Emtora Biosciences

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04375813

Brief Title

Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer Prevention

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 25, 2021 (Actual)

Primary Completion Date

January 2026 (Anticipated)

Study Completion Date

January 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Rapamycin Holdings, Inc. dba Emtora Biosciences

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-muscle Invasive Bladder Cancer

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

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, 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 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.

Masking

ParticipantInvestigator

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.

Allocation

Randomized

Enrollment

166 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active Study Drug Group

Arm Type

Active Comparator

Arm Description

Patients will be given 0.5mg eRapa (encapuslated rapamycin) orally each weekday (Monday-Friday) for one year.

Arm Title

Placebo Group

Arm Type

Placebo Comparator

Arm Description

Patients will be given a placebo (visually identical to the eRapa (encapsulated rapamycin)) orally each weekday (Monday-Friday) for one year.

Intervention Type

Drug

Intervention Name(s)

eRapa

Other Intervention Name(s)

encapsulated rapamycin

Intervention Description

0.5mg eRapa (encapsulated rapamycin) oral capsules

Intervention Type

Drug

Intervention Name(s)

Placebos

Intervention Description

placebo capsules visually identical to eRapa oral capsules

Primary Outcome Measure Information:

Title

Determine 1-year Recurrence Free Survival (RFS) rate

Description

Time Frame

1 year

Title

Change in Urinary Quality of Life

Description

Time Frame

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.

Title

Change in Cognitive Function

Description

Time Frame

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.

Title

Change in Cognitive Function

Description

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.

Time Frame

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.

Title

Change in Cognitive Function

Description

Cognitive function will be measured throughout the study period using Texas Assessment of Processing Speed (TAPS). The TAPS test will evaluate digit/symbol coding.

Time Frame

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.

Title

Change in cytoscopy consistent with recurrence (time to recurrence)

Description

Change in cytoscopy results from baseline consistent with recurrence, confirmed by pathologic examination of biopsied tissue.

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, and at year 5, with biopsies per standard of care if necessary.

Title

Change in Short Physical Performance Battery

Description

Time Frame

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.

Title

Change in Handgrip Strength

Description

Time Frame

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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. 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Cathy Grill, RN, BSN

Phone

919.452.0288

CGrill@lumabridge.com

First Name & Middle Initial & Last Name or Official Title & Degree

Leon Els, BS

Phone

919.605.6595

LEls@lumabridge.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert S Svatek, MD, MSCI

Organizational Affiliation

UT Health San Antonio

Official's Role

Principal Investigator

Facility Information:

Facility Name

UT Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Donna Mitchell

Phone

214-645-8789

donna.mitchell@utsouthwestern.edu

First Name & Middle Initial & Last Name & Degree

Jessie Williams

Phone

214-648-9195

jessica.williams2@utsouthwestern.edu

First Name & Middle Initial & Last Name & Degree

Yair Lotan, MD

Facility Name

South Texas Veterans Health Care System (recruiting for treatment at UT Health San Antonio)

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ahmed Mansour, MD

Phone

210-567-5643

Mansour@uthscsa.edu

First Name & Middle Initial & Last Name & Degree

Michael A Liss, MD

Facility Name

UT Health San Antonio

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fred Norton, BS

Phone

210-450-9630

nortonk1@uthscsa.edu

First Name & Middle Initial & Last Name & Degree

Robert S Svatek, MD

12. IPD Sharing Statement

Learn more about this trial

Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer Prevention

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