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

NCT02722538 | Completed Phase 1 FDA Drug

• 1 other identifier: TAR-200-101
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 6

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 muscle-invasive bladder cancer (MIBC) between diagnosis and radical cystectomy (RC).

Conditions

Urinary Bladder Cancer

Outcome Measures

Primary Outcomes (1)

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

  Maximum 132 days

Secondary Outcomes (30)

• Number of participants who are tolerant of TAR-200 indwelling

  From Day 0 up to Day 7

• Percentage of participants who are tolerant of TAR-200 indwelling

  From Day 0 up to Day 7

• Number of participants who are tolerant of TAR-200 indwelling

  From Day 21 up to Day 28

• Percentage of participants who are tolerant of TAR-200 indwelling

  From Day 21 up to Day 28

• Cmax, plasma dFdU

  From Day 0 up to Day 28

Study Arms (2)

Residual Tumor following TURBT

EXPERIMENTAL

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

No Residual Tumor Following TURBT

EXPERIMENTAL

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

Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 DRUG

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.

No Residual Tumor Following TURBT; Residual Tumor following TURBT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Total bilirubin ≤ 1.5xULN (upper limit of normal)
• Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5xULN
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Taris Biomedical LLC: lead

Study Sites (6)

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, United States

Location

University of Chicago Medical Center

Chicago, Illinois, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Location

Radboudumc

Nijmegen, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 35431132 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Siamak Daneshmand, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2016
• First Posted: March 30, 2016
• Study Start: May 31, 2016
• Primary Completion: May 2, 2019
• Study Completion: May 2, 2019
• Last Updated: September 18, 2023

Record last verified: 2023-09

Locations

NL (1); US (5)