A phase 1b, Multicenter, Open Label Study Evaluating Safety, Tolerability and Preliminary Efficacy of GemRIS 225mg in Subjects with Non-Muscle-Invasive Urothelial Carcinoma of the Bladder
- Conditions
- Non-Muscle-Invasive Bladder Cancer10038364
- Registration Number
- NL-OMON46132
- Lead Sponsor
- TARIS Biomedical LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
1. Age * 18 years at the time of consent.
2. Able to voluntarily give written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
3. 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.
4. Females of childbearing potential must have a negative pregnancy test.
5. Acceptable liver function defined as: bilirubin * 1.5 times upper limit of normal, and aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and alkaline phosphatase * 2.5 times upper limit of normal.
6. Acceptable renal function defined as calculated creatinine clearance * 0.58 mL/s/m2 (35 mL/min/1.73 m2).
7. Acceptable hematologic status defined as: absolute neutrophil count (ANC) * 2.5 x10^9/L (2,500 cells/mm3), platelet count * 120 x10^9/L (120,000/mm3), and hemoglobin * 6.21 mmol/L (10.0 g/dL).
8. Screening urinalysis showing no clinically significant abnormalities except those attributable to bladder cancer.
9. Not undergoing active treatment in last 3 months for prior or concurrent neoplastic disease and have fully recovered from treatment effects. Subjects undergoing concurrent hormonal therapy treatment for prostate cancer will be allowed to enroll.
10. Females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4
weeks after treatment discontinuation. Subject*s partner must also use barrier protection while subject is on study until 4 weeks after treatment discontinuation.
11. Males must be willing to use an effective method of contraception/method to avoid seminal transfer (barrier method or abstinence) from the time consent is signed until 4 weeks after treatment discontinuation. Subject*s partner(s) must also use barrier protection while subject is on study until 4 weeks after treatment discontinuation.
1. Exposure to BCG therapy and/or any other intravesical chemotherapeutic agent less than 1 year prior to enrollment, except single postoperative instillations.
2. Absence of visible tumour at Screening.
3. Any previous exposure to intravesical gemcitabine instillations within the last 12 months.
4. 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 GemRIS (i.e. bladder diverticula,
complete incontinence).
5. Documented history of vesicoureteral reflux or an indwelling ureteral stent or nephrostomy tube.
6. Subjects with a high-Grade urine cytology at recurrence.
7. Currently receiving other systemic or intravesical chemotherapy.
8. Evidence of bladder perforation during diagnostic cystoscopy.
9. Pelvic radiotherapy administered within 6 months prior to enrollment. Subjects who received radiotherapy * 6 months prior to enrollment must demonstrate no cystoscopic evidence or
clinical symptoms of radiation cystitis.
10. Bladder Post-Void Residual Volume (PVR) of > 250 mL.
11. Known hypersensitivity to gemcitabine or chemically-related drugs.
12. Known hypersensitivity to the device materials.
13. 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.
14. Use of an investigational agent within 30 days or 5 half-lives, whichever is longer, preceding Study Day 0.
15. 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.
16. History of a diagnosis of neurogenic bladder.
17. Concomitant immunosuppressive medications, such as methotrexate or TNF inhibitors, within 2 weeks of Study Day 0, exclusive of steroid doses * 5 mg daily.
18. History of any of the following within 3 months prior to the date of informed consent:
a. Major illness/major surgery (requiring hospitalization), including pelvic, lower back surgery or a procedure unrelated to bladder cancer; most outpatient procedures are not exclusionary
b. Renal or ureteral stone disease
c. Childbirth
19. 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.
20. Difficulty providing blood samples.
21. Clinically significant abnormal complete blood count (CBC), blood chemistry or urinalysis at the Screening Visit that is verified upon repeat testing.
22. 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.
23. Other unspecified reasons that, in the opinion of the Investigator or TARIS, make the subject unsuitable for enrollment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety<br /><br>For GemRIS : Safety of GemRIS upon insertion, two 7-day or 21-day dosing<br /><br>cycles, and removal.<br /><br>For Custom Inserter : Safety of the Custom Inserter during the placement of<br /><br>GemRIS.</p><br>
- Secondary Outcome Measures
Name Time Method <p>GemRIS:<br /><br>- Tolerability of GemRIS upon insertion, 7-day or 21-day dosing cycles, and<br /><br>removal.<br /><br>- Pharmacokinetic analysis of blood and urine will be performed : plasma<br /><br>gemcitabine exposure, urinary gemcitabine exposure, plasma dFdU exposure,<br /><br>urinary dFdU exposure .<br /><br>The following assessments will be performed to determine the anti-tumour effect<br /><br>of GemRIS:<br /><br>- Assessment of tumour lesion extent (area) at screening cystoscopy compared<br /><br>with cystoscopy on the day of TURBT (prior to TURBT).<br /><br>- Assessment of tumour cell death as assessed histologically by evidence of<br /><br>tumour cell apoptosis and necrosis at the time of TURBT.<br /><br>- Assessment of 2-year recurrence-free survival.<br /><br><br /><br>Custom Inserter:<br /><br>- Tolerability of the Custom Inserter during the placement of GemRIS.<br /><br>- GemRIS placement success rate as verified by post-insertion cytoscopic<br /><br>examination. </p><br>