Clinical trial NCT02720367: Safety and Tolerability of TAR-200 mg in Subjects With Non-Muscle-Invasive Bladder Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Urinary Bladder Cancer
Lead sponsor: Taris Biomedical LLC
Sponsor class: INDUSTRY
First posted: 2016-03-25
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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)


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: From the point of signing the informed consent form through last study visit, up to 59 days.
Secondary outcomes:
measure: Number of participants who are tolerant of TAR-200 indwelling (Arm 1)
timeFrame: From Day 0 up to Day 7
measure: Percentage of participants who are tolerant of TAR-200 indwelling (Arm 1)
timeFrame: From Day 0 up to Day 7
measure: Number of participants who are tolerant of TAR-200 indwelling (Arm 1)
timeFrame: From Day 21 up to Day 28
measure: Percentage of participants who are tolerant of TAR-200 indwelling (Arm 1)
timeFrame: From Day 21 up to Day 28
measure: Cmax, plasma dFdU (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Tmax, plasma dFdU (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Cavg, plasma dFdU (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Cmax, plasma dFdC (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Tmax, plasma dFdC (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Cavg, plasma dFdC (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Cmax, urine dFdU (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Tmax, urine dFdU (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Cavg, urine dFdU (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Cmax, urine dFdC (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Tmax, urine dFdC (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: Cavg, urine dFdC (Arm 1)
timeFrame: From Day 0 up to Day 32
measure: 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)
timeFrame: Anti-tumor analysis will occur at the following study day visit Day 28
measure: Number of participants who are tolerant of TAR-200 indwelling (Arm 2)
timeFrame: From Day 0 up to Day 21
measure: Percentage of participants who are tolerant of TAR-200 indwelling (Arm 2)
timeFrame: From Day 0 up to Day 21
measure: Number of participants who are tolerant of TAR-200 indwelling (Arm 2)
timeFrame: From Day 21 up to Day 42
measure: Percentage of participants who are tolerant of TAR-200 indwelling (Arm 2)
timeFrame: From Day 21 up to Day 42
measure: Cmax, plasma dFdU (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Tmax, plasma dFdU (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Cavg, plasma dFdU (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Cmax, plasma dFdC (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Tmax, plasma dFdC (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Cavg, plasma dFdC (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Cmax, urine dFdU (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Tmax, urine dFdU (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Cavg, urine dFdU (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Cmax, urine dFdC (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Tmax, urine dFdC (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: Cavg, urine dFdC (Arm 2)
timeFrame: From Day 0 up to Day 47
measure: 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)
timeFrame: Anti-tumor analysis will occur at the following study day visit Day 42
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Radboudumc
Study officials:
affiliation: Radboud University Medical Center
name: Johannes Witjes, MD
role: PRINCIPAL_INVESTIGATOR
References: