Bladder Cancer Clinical Trials

• Histologically proven high risk non-muscle invasive bladder cancer (NMIBC)

• Adequate archival tissue sample available for histological assessment (date sample taken must be within 6 months of planned start of treatment)

• Predominant histologic component (\> 50%) must be urothelial (transitional cell) carcinoma

• Bacillus Calmette-Guerin (BCG) unresponsive disease or are intolerant of BCG therapy

• Refused or deemed clinically inappropriate for radical cystectomy

• ≥18 years of age

• Body weight \>30 kg

• World Health Organisation (WHO) performance status 0-1

• Must have undergone each of the following procedures within 8 weeks of registration:

‣ Complete excision of all papillary disease (T1/TaHG) and demonstration of no muscle invasive disease in the resected specimens (muscle must be present in the tumour sample)

⁃ Bladder 'Mapping biopsies' taken

⁃ CT of the chest

⁃ CT Urogram or MRI of the abdomen and pelvis (if CT is not possible)

⁃ Adequate haematological status:

∙ Haemoglobin ≥9.0 g/dL

‣ Absolute neutrophil count ≥1.5 x 10\^9/L (≥150,000 per mm3)

‣ Platelet count ≥100 x 10\^9/L (≥100,000 per mm3)

‣ International Normalised Ratio (INR) ≤1.5 and Activated Partial Thromoplastin Time (APTT) ≤1.5 x Upper Limit Normal (ULN). NB: This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.

⁃ Adequate liver function:

∙ Total bilirubin ≤1.5 X ULN (\<3.0 x ULN for patients with Gilbert's syndrome)

‣ Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≤2.5 x ULN

⁃ Adequate renal function: Measured creatinine clearance ≥40 mL/min or calculated creatinine clearance ≥40 mL/min using Cockcroft-Gault formula.

⁃ Life expectancy of ≥6 months

⁃ Willing and able to give informed consent (which includes compliance with the requirements and restrictions listed in the patient information sheet (PIS) and in this protocol). NB: Consent must be obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.

⁃ Patients of child-bearing potential and male patients with female partners of child-bearing potential must agree to use highly effective contraception methods from date of consent, which must be continued for up to 90 days after last treatment administration.

⁃ Female patients must not be pregnant. There should be sufficient evidence of post-menopausal status or a negative serum pregnancy test for pre-menopausal female patients.

⁃ Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and any other study procedures.