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Trial record 3 of 4 for:    TAR-200

Safety and Tolerability of TAR-200 mg in Subjects With Non-Muscle-Invasive Bladder Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02720367
Recruitment Status : Active, not recruiting
First Posted : March 25, 2016
Last Update Posted : April 19, 2019
Sponsor:
Information provided by (Responsible Party):
Taris Biomedical LLC

Brief Summary:
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)

Condition or disease Intervention/treatment Phase
Urinary Bladder Cancer Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2016
Actual Primary Completion Date : January 2018
Estimated Study Completion Date : January 2020


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.
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.




Primary Outcome Measures :
  1. 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. ]

Secondary Outcome Measures :
  1. Number of participants who are tolerant of TAR-200 indwelling (Arm 1) [ Time Frame: From Day 0 up to Day 7 ]
  2. Percentage of participants who are tolerant of TAR-200 indwelling (Arm 1) [ Time Frame: From Day 0 up to Day 7 ]
  3. Number of participants who are tolerant of TAR-200 indwelling (Arm 1) [ Time Frame: From Day 21 up to Day 28 ]
  4. Percentage of participants who are tolerant of TAR-200 indwelling (Arm 1) [ Time Frame: From Day 21 up to Day 28 ]
  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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 ]
  18. Number of participants who are tolerant of TAR-200 indwelling (Arm 2) [ Time Frame: From Day 0 up to Day 21 ]
  19. Percentage of participants who are tolerant of TAR-200 indwelling (Arm 2) [ Time Frame: From Day 0 up to Day 21 ]
  20. Number of participants who are tolerant of TAR-200 indwelling (Arm 2) [ Time Frame: From Day 21 up to Day 42 ]
  21. Percentage of participants who are tolerant of TAR-200 indwelling (Arm 2) [ Time Frame: From Day 21 up to Day 42 ]
  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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

  27. 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.

  28. 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.

  29. 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

  30. 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.

  31. 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.

  32. 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.

  33. 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

  34. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • 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.

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): NCT02720367


Locations
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Netherlands
Canisius Wilhelmina Ziekenhuis
Nijmegen, Netherlands
Radboudumc
Nijmegen, Netherlands
Sponsors and Collaborators
Taris Biomedical LLC
Investigators
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Principal Investigator: Johannes Witjes, MD Radboud University

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Responsible Party: Taris Biomedical LLC
ClinicalTrials.gov Identifier: NCT02720367     History of Changes
Other Study ID Numbers: TAR-200-102
2016-000099-66 ( EudraCT Number )
First Posted: March 25, 2016    Key Record Dates
Last Update Posted: April 19, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
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
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs