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CompletedNCT02722538Updated Sep 18, 2023

Safety and Tolerability of GemRIS 225 mg in Subjects With Muscle-Invasive Bladder Cancer

A Phase 1 interventional study of Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 in Urinary Bladder Cancer, sponsored by Taris Biomedical LLC. Completed at 6 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-09-18.

Sponsored by Taris Biomedical LLC · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Primary completion was May 2019, 7 years 5 months ago, and no results have been posted to the registry.
Phase
Phase 1
Study type
Interventional
Enrollment
23
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to determine if TAR-200, an investigational drug-delivery system, is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) between diagnosis and radical cystectomy (RC).

02

Conditions studied

  • Urinary Bladder Cancer
03

In context

Urinary Bladder Neoplasms

1,616 studies on the registry are indexed under Urinary Bladder Neoplasms; 421 are open to participants now.

This study's enrollment of 23 is below the median of 60 across 1,163 interventional studies indexed under Urinary Bladder Neoplasms.

Browse Urinary Bladder Neoplasms studies →

Lead sponsor

Taris Biomedical LLC is the lead sponsor of 5 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-III). Subjects with evidence of metastatic nodal disease to the obuturator or presacral lymph nodes only may be included (N1 M0). Subjects with any degree of fixation of the pelvic sidewall are not eligible.
  • In Arm 1, subjects must have residual visible tumor following TURBT. In Arm 2, subjects must be fully resected (i.e., no visible tumor or as little tumor as possible) after restaging TURBT 2-6 weeks prior to Study Day 0.

  • Adequate bone marrow, liver, and renal function, as assessed by the following requirements conducted within 21 days prior to dosing:

    1. Hemoglobin ≥ 9.0 g/dL
    2. Absolute neutrophil count (ANC) ≥ 1,500/mm3
    3. Platelet count ≥ 100,000/mm3
    4. Total bilirubin ≤ 1.5xULN (upper limit of normal)
    5. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5xULN
    6. Glomerular Filtration Rate (GFR) ≥ 30% (≥ 30 ml/min/1.73 m2)
  • Subjects must be willing to undergo a cystoscopy on study for investigational product removal.
  • Eligible for and willing to undergo RC per the attending urologist.
  • Subjects must be deemed ineligible for cisplatin-based combination chemotherapy by the attending medical oncologist.
  • Subjects medically eligible for neoadjuvant cisplatin-based combination chemotherapy who refuse this therapeutic option and understand the risks and benefits of doing so.
  • Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder.
  • Written informed consent and Health Insurance Portability and Accountability Act of 1966 (HIPAA) authorization for release of personal health information.
  • Age > 18 years at the time of consent.

Exclusion criteria

Exclusion Criteria:

  • Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome.
  • Prior systemic chemotherapy for transitional cell carcinoma of the bladder. Any other prior systemic chemotherapy for a non-urothelial carcinoma must have been completed > 5 years prior to initiation of study.
  • Previous exposure to gemcitabine instillations.
  • Currently receiving other intravesical chemotherapy.
  • Concurrent clinically significant infections as determined by the treating investigator.
  • Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use or removal of TAR-200.
  • Documented history of vesicoureteral reflux or the presence of an indwelling ureteral stent or nephrostomy tube at the time of screening.
  • Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥ 6 months prior to enrollment must demonstrate no cystoscopic evidence or 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 that in the opinion of the investigator, contraindicates participation. 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.
  • History of diagnosis of neurogenic bladder.
  • Concomitant immunosuppressive medications, such as methotrexate or TNF inhibitors, within 2 weeks of Study Day 0, exclusive of steroid doses ≤ 5 mg daily.
  • Difficulty providing blood samples.
  • 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 subject unsuitable for enrollment.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
23 participants (actual)

Study arms

  • Experimental
    Residual Tumor following TURBT

    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 Radical Cystectomy (RC).

    Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200

  • Experimental
    No Residual Tumor Following TURBT

    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 Radical Cystectomy (RC).

    Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200

Interventions

  • DrugGemcitabine-Releasing Intravesical System (GemRIS)/TAR-200

    TAR-200 is a passive, nonresorbable gemcitabine-releasing intravesical drug delivery system, regulated as a drug, whose primary mode of action is the controlled release of gemcitabine into the bladder over a 7-day period.

06

What researchers measure

Primary outcomes

  1. Number of participants with treatment emergent adverse events (TEAEs) coded with MedDRA and graded for severity with CTCAE v4.0

    Time frame: Maximum 132 days

Secondary outcomes

  1. Number of participants who are tolerant of TAR-200 indwelling

    Time frame: From Day 0 up to Day 7

  2. Percentage of participants who are tolerant of TAR-200 indwelling

    Time frame: From Day 0 up to Day 7

  3. Number of participants who are tolerant of TAR-200 indwelling

    Time frame: From Day 21 up to Day 28

  4. Percentage of participants who are tolerant of TAR-200 indwelling

    Time frame: From Day 21 up to Day 28

  5. Cmax, plasma dFdU

    Analysis of Cmax (maximum concentration achieved over time) of diflourodeoxyuridine (dFdU) in plasma.

    Time frame: From Day 0 up to Day 28

  6. Tmax, plasma dFdU

    Analysis of Tmax (Day at which maximum concentration was achieved) of diflourodeoxyuridine (dFdU) in plasma.

    Time frame: From Day 0 up to Day 28

  7. Cavg, plasma dFdU

    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

    Time frame: From Day 0 up to Day 28

  8. Cmax, plasma dFdC

    Analysis of Cmax (maximum concentration achieved over time) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in plasma

    Time frame: From Day 0 up to Day 28

  9. Tmax, plasma dFdC

    Analysis of Tmax (Day at which maximum concentration was achieved) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in plasma

    Time frame: From Day 0 up to Day 28

  10. Cavg, plasma dFdC

    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

    Time frame: From Day 0 up to Day 28

  11. Cmax, urine dFdU (Arm 1 only)

    Analysis of Cmax (maximum concentration achieved over time) of diflourodeoxyuridine (dFdU) in urine

    Time frame: From Day 0 up to Day 28

  12. Tmax, urine dFdU (Arm 1 only)

    Analysis of Cmax (maximum concentration achieved over time) of diflourodeoxyuridine (dFdU) in urine

    Time frame: From Day 0 up to Day 28

  13. Cavg, urine dFdU (Arm 1 only)

    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

    Time frame: From Day 0 up to Day 28

  14. Cmax, urine dFdC (Arm 1 only)

    Analysis of Cmax (maximum concentration achieved over time) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in urine

    Time frame: From Day 0 up to Day 28

  15. Tmax, urine dFdC (Arm 1 only)

    Analysis of Tmax (Day at which maximum concentration was achieved) of gemcitabine (deoxydifluorocytidine hydrochloride - dFdC) in urine

    Time frame: From Day 0 up to Day 28

  16. Cavg, urine dFdC (Arm 1 only)

    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.

    Time frame: From Day 0 up to Day 28

  17. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (AKT) (Arm 1)

    Time frame: Anti-tumor analysis will occur at study visit Day 28.

  18. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD31) (Arm 1)

    Time frame: Anti-tumor analysis will occur at study visit Day 28.

  19. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (Ki67) (Arm 1)

    Time frame: Anti-tumor analysis will occur at study visit Day 28.

  20. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (TUNEL) (Arm 1)

    Time frame: Anti-tumor analysis will occur at study visit Day 28.

  21. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD4) (Arm 1)

    Time frame: Anti-tumor analysis will occur at study visit Day 28.

  22. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD8) (Arm 1)

    Time frame: Anti-tumor analysis will occur at study visit Day 28.

  23. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (PD-L1) (Arm 1)

    Time frame: Anti-tumor analysis will occur at study visit Day 28.

  24. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (AKT) (Arm 2)

    Time frame: Anti-tumor analysis will occur at study visit Day 42.

  25. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD31) (Arm 2)

    Time frame: Anti-tumor analysis will occur at study visit Day 42.

  26. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (Ki67) (Arm 2)

    Time frame: Anti-tumor analysis will occur at study visit Day 42.

  27. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (TUNEL) (Arm 2)

    Time frame: Anti-tumor analysis will occur at study visit Day 42.

  28. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD4) (Arm 2)

    Time frame: Anti-tumor analysis will occur at study visit Day 42.

  29. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD8) (Arm 2)

    Time frame: Anti-tumor analysis will occur at study visit Day 42.

  30. Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (PD-L1) (Arm 2)

    Time frame: Anti-tumor analysis will occur at study visit Day 42.

07

Study locations

6 sites
  • University of Southern California Norris Comprehensive Cancer Center
    Los Angeles, California, United States
  • University of Chicago Medical Center
    Chicago, Illinois, United States
  • Johns Hopkins Hospital
    Baltimore, Maryland, United States
  • Columbia University Medical Center
    New York, New York 10032, United States
  • Ohio State University Wexner Medical Center
    Columbus, Ohio, United States
  • Radboudumc
    Nijmegen, Netherlands
08

References and documents

Publications

  • Daneshmand S, Brummelhuis ISG, Pohar KS, Steinberg GD, Aron M, Cutie CJ, Keegan KA, Maffeo JC, Reynolds DL, Raybold B, Chau A, Witjes JA. The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) in muscle-invasive bladder cancer patients: a phase I trial. Urol Oncol. 2022 Jul;40(7):344.e1-344.e9. doi: 10.1016/j.urolonc.2022.02.009. Epub 2022 Apr 14. PubMed 35431132 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 18, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02722538
Lead sponsor
Taris Biomedical LLC
Responsible party
Sponsor
First posted
Mar 30, 2016
Start date
May 31, 2016
Primary completion
May 2, 2019
Completion
May 2, 2019
Last update
Sep 18, 2023

Study contacts

Siamak Daneshmand, MD
principal investigator · University of Southern California

Oversight

FDA-regulated drug
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Sep 2023. You cannot join it, but the record below documents what was studied.

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