A research study of an investigational drug delivery system for adults with high-risk non-muscle invasive bladder cancer
- Conditions
- Recurrent high-risk non-muscle-invasive bladder cancerCancer
- Registration Number
- ISRCTN72352492
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 250
1. 18 or more years of age at the time of informed consent.
2. Histologically confirmed diagnosis by local pathology (within 90 days of documented informed consent) of recurrent, papillary-only high-risk non-muscle-invasive bladder cancer (HR-NMIBC; defined as high-grade [HG] Ta or any T1; no carcinoma in situ [CIS]).
3. Participants with variant histologic subtypes are allowed if tumour(s) demonstrate urothelial (transitional cell histology) predominance. However, neuroendocrine and small cell variants will be excluded.
4. All visible tumour completely resected prior to randomisation. Urine cytology must not be positive or suspicious for HG urothelial carcinoma (UC) before randomisation. For participants with lamina propria invasion (T1) on the Screening biopsy/ transurethral resection of bladder tumour (TURBT), muscularis propria must be present to rule out muscle-invasive bladder cancer (MIBC).
5. Participants must have received at least 5 of 6 induction doses of Bacillus Calmette-Guérin (BCG; adequate induction) with or without maintenance therapy.
6. Diagnosis of recurrent, papillary-only HR-NMIBC (defined as HG Ta or any T1; no CIS) must be within 12 months of the last dose of BCG therapy.
7. Participants must be ineligible for or have elected not to undergo radical cystectomy (RC).
8. All adverse events (AEs) associated with any prior surgery and intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade less than or equal to 2 prior to Screening.
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0, 1, or 2.
10. Adequate bone marrow, liver, and renal function, as defined in the study protocol.
11. While on study treatment and for 6 months after the last dose of study treatment, a participant must: not breastfeed or be pregnant; not donate gametes (i.e., eggs or sperm) or freeze for future use for the purposes of assisted reproduction; wear an external condom; if of childbearing potential’ have a negative highly sensitive pregnancy test at Screening and within 24 hours before the first dose of study treatment, and agree to further pregnancy tests; practice at least 1 highly effective method of contraception (if oral contraceptives are used, a barrier method of contraception must also be used); if a participant’s partner is of childbearing potential, the partner must practice a highly effective method of contraception unless the participant is vasectomised.
12. Participants must sign an Informed Consent Form (ICF; or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study and agreement to store samples when applicable.
13. Participants must be willing to comply with and able to undergo all study procedures and willing and able to adhere to the lifestyle restrictions specified in the protocol.
1. Presence of carcinoma in situ (CIS) at any point from time of diagnosis of papillary-only high-risk non-muscle-invasive bladder cancer (HR-NMIBC) recurrence to randomisation. Additionally, presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (UC).
2. Must not currently have UC or histological variant at any site outside of the urinary bladder. UC of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to randomisation with no evidence of recurrence.
3. N+ and/or M+ per blinded independent central review (BICR) of CT/MR Urography.
4. Active malignancies other than the disease being treated under study. Allowed recent second or prior malignancies are detailed in the protocol.
5. 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. Participants with tumours involving the prostatic urethra in men will be excluded.
6. A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4,000 millilitres (mL).
7. History of uncontrolled cardiovascular disease in the preceding 3 months prior to Screening.
8. Pyeloureteral tube externalised to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted if it does not interfere with either insertion or retention of TAR-200 into the bladder. Bilateral ureteral stents are exclusionary.
9. Participants who have not recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomisation (transurethral resection of bladder tumour [TURBT] is not considered major surgery).
10. Indwelling catheters are not permitted; however, intermittent catheterisation is acceptable.
11. Concurrent urinary tract infection (UTI) as defined within the protocol.
12. Uncontrolled intercurrent illness.
13. As determined by the Investigator, contraindications to the use of TAR-200, mitomycin C (MMC), or gemcitabine per local prescribing information. Known hypersensitivity to any study component.
14. Received a live virus vaccine within 30 days prior to randomisation. Inactivated (non-live or non-replicating) vaccines approved or authorised for emergency use (e.g., for COVID-19) by local health authorities are allowed.
15. Received serial intravesical therapy or systemic therapy from the time of histologic diagnosis of recurrent HR-NMIBC to date of randomisation. Immediate post-TURBT single-dose per-operative intravesical chemotherapy is allowed in accordance with institutional guidelines.
16. Previous treatment with TAR-200.
17. Currently participating or has participated in a study and received an investigational agent or investigational device within 4 weeks prior to Screening.
18. Participants with evidence of bladder perforation during cystoscopy. Participants are eligible if perforation has resolved prior to dosing.
19. Bladder post-void residual (PVR) volume greater than 350 mL at Screening after second voided urine.
20. Any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method