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

Phase 1CompletedNCT02720367

Taris Biomedical LLC12 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Urinary Bladder Cancer

Interventions

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

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (2)

Canisius Wilhelmina Ziekenhuis

Nijmegen, Netherlands

Radboudumc

Nijmegen, Netherlands

Outcomes

Primary Outcomes

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 Outcomes

Number of participants who are tolerant of TAR-200 indwelling (Arm 1)

Time frame: 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

Number of participants who are tolerant of TAR-200 indwelling (Arm 1)

Time frame: 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

Cmax, plasma dFdU (Arm 1)

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

Time frame: From Day 0 up to Day 32

Tmax, plasma dFdU (Arm 1)

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

Time frame: From Day 0 up to Day 32

Cavg, plasma dFdU (Arm 1)

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 32

Data from ClinicalTrials.gov

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Cmax, plasma dFdC (Arm 1)

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

Time frame: From Day 0 up to Day 32

Tmax, plasma dFdC (Arm 1)

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 32

Cavg, plasma dFdC (Arm 1)

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 32

Cmax, urine dFdU (Arm 1)

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

Time frame: From Day 0 up to Day 32

Tmax, urine dFdU (Arm 1)

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

Time frame: From Day 0 up to Day 32

Cavg, urine dFdU (Arm 1)

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 32

Cmax, urine dFdC (Arm 1)

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

Time frame: From Day 0 up to Day 32

Tmax, urine dFdC (Arm 1)

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 32

Cavg, urine dFdC (Arm 1)

Time frame: 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

Number of participants who are tolerant of TAR-200 indwelling (Arm 2)

Time frame: 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

Number of participants who are tolerant of TAR-200 indwelling (Arm 2)

Time frame: 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

Cmax, plasma dFdU (Arm 2)

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