Ensayos clínicos

Inclusion Criteria:

• Histological proof of muscle-invasive urothelial carcinoma of the bladder (cT2-cT3b, N0, M0). Subjects with mixed histology are required to have documented dominant transitional cell pattern with no more than 10% squamous differentiation and 10% glandular differentiation.  Micropapillary/sarcomatoid/adenocarcinoma variants are not allowed.
• Subject must have been as fully resected as possible per the physician’s judgment.
• Subjects must be deemed unfit for RC due to comorbid conditions with a risk of mortality due to RC ≥3% as estimated by the American College of Surgeons risk calculator using the current procedure terminology code 51595 or 51596 for cystectomy (http://riskcalculator.facs.org/RiskCalculator/PatientInfo.jsp).
• Subjects must refuse cisplatin-based chemotherapy (and understand the risk and benefits of doing so) or be deemed ineligible for cisplatin-based chemotherapy by meeting at least one of the following criteria:
  • World Health Organization (WHO) or Eastern Cooperative Oncology Group (ECOG) performance status of ≥2 or Karnofsky performance status of 60-70%;
  • Creatinine clearance (calculated or measured) ≤ 60 mL/min;
  • Common Terminology Criteria for Adverse Events (CTCAE) version 5.0;
  • Grade ≥2 audiometric hearing loss;
  • CTCAE version 5.0 Grade ≥ 2 peripheral neuropathy;
  • New York Heart Association ≥ Class III heart failure.
• Subject must not be eligible for or is refusing radical radiotherapy ≥ 50 Gy.
• Life expectancy of at least 4 months.
• Adequate bone marrow, liver, and renal function, as assessed by the following requirements conducted within 28 days prior to dosing:
  • Hemoglobin ≥ 7.0 g/dL;
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3;
  • Platelet count ≥ 75,000/mm^3;
  • Total bilirubin ≤ 2x the upper limit of normal (ULN);
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN;
  • Glomerular filtration rate ≥ 30% (≥ 30 ml/min/1.73 m^2).
• Subjects must be willing to undergo a cystoscopy for Investigational Product placement and removal.
• Subjects must be willing to undergo a biopsy at 3 months for assessment of clinical response.
• Written informed consent and authorization for release of personal health information obtained according to local laws.
• Age ≥ 18 years at the time of informed consent.
• 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.
• 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 must also use barrier protection while subject is on study until 4 weeks after treatment discontinuation.
• Females of childbearing potential must have a negative pregnancy test within 28 days prior to Study Day 0.

Exclusion Criteria:

• Other active malignancies within 12 months except for those with a negligible risk of metastasis or death treated with expected curative outcome.  Subjects with prostate cancer who are managed with active surveillance will be allowed. Subjects with concomitant upper tract urothelial carcinoma are excluded.
• Prior systemic chemotherapy for urothelial cell carcinoma of the bladder.
  • Note: prior systemic chemotherapy administered for radio-sensitizing purposes is acceptable.
• Pelvic radiotherapy administered within less than 6 months prior to enrollment.
  • Note: subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis.
• 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.
• Pyeloureteral tube externalized to the skin is exclusionary. Ureteral stent or unilateral nephrostomy tube is allowed.
• Indwelling catheters are not permitted.
• Evidence of bladder perforation during diagnostic cystoscopy.
• Bladder post-void residual volume (PVR) of > 750 mL.
• Concurrent clinically significant infections as determined by the treating Investigator including active, uncontrolled urogenital bacterial, viral, or fungal infections, including urinary tract infection. Skin/nail fungal infections are not exclusionary.
• Known hypersensitivity to gemcitabine (or other drug excipients) or chemically-related drugs.
• Known hypersensitivity to the device constituent or TARIS Inserter materials.
• Use of an investigational product within 30 days or 5 half-lives, whichever is longer, preceding Study Day 0.
• Female subject who is lactating/breastfeeding.
• 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, make the subject unsuitable for enrollment.