- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02720367
Safety and Tolerability of TAR-200 mg in Subjects With Non-Muscle-Invasive Bladder Cancer
March 9, 2020 updated by: Taris Biomedical LLC
A Phase 1b, Multicenter, Open Label Study Evaluating Safety, Tolerability and Preliminary Efficacy of GemRIS 225 mg in Subjects With Non-Muscle-Invasive Urothelial Carcinoma of the Bladder
The purpose of this study is to determine if TAR-200, an investigational drug-delivery system is safe and tolerable in patients with recurrent low or intermediate risk non-muscle-invasive bladder cancer (NMIBC) between diagnosis and transurethral resection of bladder tumors (TURBT)
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
12
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Nijmegen, Netherlands
- Radboudumc
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Nijmegen, Netherlands
- Canisius Wilhelmina Ziekenhuis
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- A documented history of histologically-confirmed low or intermediate risk urothelial carcinoma of the bladder, excluding carcinoma in situ (pTis), pathologic stage pT1 (invasive into lamina propria) and high-Grade disease, judged not to be muscle infiltrating (pT2 or greater) and accessible for resection.
- Adequate laboratory parameters.
- Screening urinalysis showing no clinically significant abnormalities except those attributable to bladder cancer.
- Not undergoing active treatment in last 3 months for prior or concurrent neoplastic disease and have fully recovered from treatment effects. Patients undergoing concurrent hormonal therapy treatment for prostate cancer will be allowed to enroll.
Exclusion Criteria:
- Exposure to BCG therapy and/or any other intravesical. chemotherapeutic agent less than 1 year prior to enrollment, except single postoperative instillations.
- Absence of visible tumor at Screening.
- Any previous exposure to intravesical gemcitabine instillations within the past 12 months.
- Presence of any bladder or urethral anatomical feature that in the opinion of the investigator may prevent the safe placement, indwelling use or removal of TAR-200 (i.e. bladder diverticula, complete incontinence).
- Patients with a high-Grade urine cytology at recurrence.
- Currently receiving other systemic or intravesical chemotherapy.
- Pelvic radiotherapy administered within 6 months prior to enrollment. Patients who received radiotherapy ≥ 6 months prior to enrollment must demonstrate no cystoscopic evidence or clinical symptoms of radiation cystitis.
- Bladder Post-Void Residual Volume (PVR) of > 250-mL.
- Active, uncontrolled urogenital bacterial, viral, or fungal infections, including urinary tract infection. Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study.
- History or presence of any significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, gynecological, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder that, in the opinion of the investigator, contraindicates participation.
- Concomitant immunosuppressive medications, such as methotrexate or TNF inhibitors, within 2 weeks of Study Day 0, exclusive of steroid doses ≤5 mg daily.
- Female subject who is pregnant (as verified by urine test at time of screening) or lactating, or of childbearing potential and not using acceptable methods of contraception.
- Unwilling or unable to provide informed consent or comply with the requirements of this protocol, including the presence of any condition (physical, mental or social) that is likely to affect the subject's return for scheduled visits and follow-up.
- Other unspecified reasons that, in the opinion of the investigator or TARIS, make the patient unsuitable for enrollment.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 7-Day Regimen
TAR-200 is placed into the bladder through an inserter on Study Day 0 and is removed on Study Day 7. TAR-200 releases gemcitabine gradually during the 7 day indwelling time.
A second TAR-200 is placed in the bladder on Study Day 21 and is removed on Study Day 28, which is the day of the TURBT.
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TAR-200 is a passive, nonresorbable gemcitabine-releasing intravesical system whose primary mode of action is the controlled release of gemcitabine into the bladder over an indwelling period.
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Experimental: 21-Day Regimen
TAR-200 is placed into the bladder through an inserter on Study Day 0 and is removed on Study Day 21.
TAR-200 releases gemcitabine gradually during the 21 day indwelling time.
A second TAR-200 is placed in the bladder on Study Day 21 and is removed on Study Day 42.
|
TAR-200 is a passive, nonresorbable gemcitabine-releasing intravesical system whose primary mode of action is the controlled release of gemcitabine into the bladder over an indwelling period.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety as defined by the number of participants with treatment emergent adverse events (TEAEs) coded with MedDRA and graded for severity with CTCAE v4.0
Time Frame: From the point of signing the informed consent form through last study visit, up to 59 days.
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From the point of signing the informed consent form through last study visit, up to 59 days.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants who are tolerant of TAR-200 indwelling (Arm 1)
Time Frame: From Day 0 up to Day 7
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From Day 0 up to Day 7
|
|
Percentage of participants who are tolerant of TAR-200 indwelling (Arm 1)
Time Frame: From Day 0 up to Day 7
|
From Day 0 up to Day 7
|
|
Number of participants who are tolerant of TAR-200 indwelling (Arm 1)
Time Frame: From Day 21 up to Day 28
|
From Day 21 up to Day 28
|
|
Percentage of participants who are tolerant of TAR-200 indwelling (Arm 1)
Time Frame: From Day 21 up to Day 28
|
From Day 21 up to Day 28
|
|
Cmax, plasma dFdU (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Cmax (maximum concentration achieved over time) of diflourodeoxyuridine (dFdU) in plasma.
|
From Day 0 up to Day 32
|
Tmax, plasma dFdU (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Tmax (Day at which maximum concentration was achieved) of diflourodeoxyuridine (dFdU) in plasma.
|
From Day 0 up to Day 32
|
Cavg, plasma dFdU (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Descriptive statistics (e.g.
sample size, mean and median, quartiles, minimum and maximum and box plots) of the concentration of diflourodeoxyuridine (dFdU) in plasma.
|
From Day 0 up to Day 32
|
Cmax, plasma dFdC (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Cmax (maximum concentration achieved over time) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in plasma.
|
From Day 0 up to Day 32
|
Tmax, plasma dFdC (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Tmax (Day at which maximum concentration was achieved) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in plasma
|
From Day 0 up to Day 32
|
Cavg, plasma dFdC (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Descriptive statistics (e.g.
sample size, mean and median, quartiles, minimum and maximum and box plots) of the concentration of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in plasma.
|
From Day 0 up to Day 32
|
Cmax, urine dFdU (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Cmax (maximum concentration achieved over time) of diflourodeoxyuridine (dFdU) in urine.
|
From Day 0 up to Day 32
|
Tmax, urine dFdU (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Tmax (Day at which maximum concentration was achieved) of diflourodeoxyuridine (dFdU) in urine
|
From Day 0 up to Day 32
|
Cavg, urine dFdU (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Descriptive statistics (e.g.
sample size, mean and median, quartiles, minimum and maximum and box plots) of the concentration of diflourodeoxyuridine (dFdU) in urine.
|
From Day 0 up to Day 32
|
Cmax, urine dFdC (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Cmax (maximum concentration achieved over time) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in urine.
|
From Day 0 up to Day 32
|
Tmax, urine dFdC (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Tmax (Day at which maximum concentration was achieved) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in urine.
|
From Day 0 up to Day 32
|
Cavg, urine dFdC (Arm 1)
Time Frame: From Day 0 up to Day 32
|
Analysis of Descriptive statistics (e.g.
sample size, mean and median, quartiles, minimum and maximum and box plots) of the concentration of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in urine
|
From Day 0 up to Day 32
|
Preliminary anti-tumor effects will be assessed in tumor material (post-treatment) for assessment of immunohistochemical tissue biomarkers of drug-induced cell death (AKT, CD31, Ki67, TUNEL). (Arm 1)
Time Frame: Anti-tumor analysis will occur at the following study day visit Day 28
|
Anti-tumor analysis will occur at the following study day visit Day 28
|
|
Number of participants who are tolerant of TAR-200 indwelling (Arm 2)
Time Frame: From Day 0 up to Day 21
|
From Day 0 up to Day 21
|
|
Percentage of participants who are tolerant of TAR-200 indwelling (Arm 2)
Time Frame: From Day 0 up to Day 21
|
From Day 0 up to Day 21
|
|
Number of participants who are tolerant of TAR-200 indwelling (Arm 2)
Time Frame: From Day 21 up to Day 42
|
From Day 21 up to Day 42
|
|
Percentage of participants who are tolerant of TAR-200 indwelling (Arm 2)
Time Frame: From Day 21 up to Day 42
|
From Day 21 up to Day 42
|
|
Cmax, plasma dFdU (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Cmax (maximum concentration achieved over time) of diflourodeoxyuridine (dFdU) in plasma.
|
From Day 0 up to Day 47
|
Tmax, plasma dFdU (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Tmax (Day at which maximum concentration was achieved) of diflourodeoxyuridine (dFdU) in plasma.
|
From Day 0 up to Day 47
|
Cavg, plasma dFdU (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Descriptive statistics (e.g.
sample size, mean and median, quartiles, minimum and maximum and box plots) of the concentration of diflourodeoxyuridine (dFdU) in plasma.
|
From Day 0 up to Day 47
|
Cmax, plasma dFdC (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Cmax (maximum concentration achieved over time) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in plasma.
|
From Day 0 up to Day 47
|
Tmax, plasma dFdC (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Tmax (Day at which maximum concentration was achieved) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in plasma
|
From Day 0 up to Day 47
|
Cavg, plasma dFdC (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Descriptive statistics (e.g.
sample size, mean and median, quartiles, minimum and maximum and box plots) of the concentration of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in plasma.
|
From Day 0 up to Day 47
|
Cmax, urine dFdU (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Cmax (maximum concentration achieved over time) of diflourodeoxyuridine (dFdU) in urine.
|
From Day 0 up to Day 47
|
Tmax, urine dFdU (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Tmax (Day at which maximum concentration was achieved) of diflourodeoxyuridine (dFdU) in urine
|
From Day 0 up to Day 47
|
Cavg, urine dFdU (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Descriptive statistics (e.g.
sample size, mean and median, quartiles, minimum and maximum and box plots) of the concentration of diflourodeoxyuridine (dFdU) in urine.
|
From Day 0 up to Day 47
|
Cmax, urine dFdC (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Cmax (maximum concentration achieved over time) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in urine.
|
From Day 0 up to Day 47
|
Tmax, urine dFdC (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Tmax (Day at which maximum concentration was achieved) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in urine.
|
From Day 0 up to Day 47
|
Cavg, urine dFdC (Arm 2)
Time Frame: From Day 0 up to Day 47
|
Analysis of Descriptive statistics (e.g.
sample size, mean and median, quartiles, minimum and maximum and box plots) of the concentration of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in urine
|
From Day 0 up to Day 47
|
Preliminary anti-tumor effects will be assessed in tumor material (post-treatment) for assessment of immunohistochemical tissue biomarkers of drug-induced cell death (AKT, CD31, Ki67, TUNEL). (Arm 2)
Time Frame: Anti-tumor analysis will occur at the following study day visit Day 42
|
Anti-tumor analysis will occur at the following study day visit Day 42
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Johannes Witjes, MD, Radboud University Medical Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 1, 2016
Primary Completion (Actual)
January 1, 2018
Study Completion (Actual)
March 1, 2020
Study Registration Dates
First Submitted
February 25, 2016
First Submitted That Met QC Criteria
March 21, 2016
First Posted (Estimate)
March 25, 2016
Study Record Updates
Last Update Posted (Actual)
March 10, 2020
Last Update Submitted That Met QC Criteria
March 9, 2020
Last Verified
March 1, 2020
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
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gemcitabine
Other Study ID Numbers
- TAR-200-102
- 2016-000099-66 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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