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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Netherlands
      • Nijmegen, Netherlands
        • Radboudumc
      • Nijmegen, Netherlands
        • Canisius Wilhelmina Ziekenhuis

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200
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.
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.
Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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.
From the point of signing the informed consent form through last study visit, up to 59 days.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Taris Biomedical LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 25, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 21, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 10, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 9, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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