Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer

Inclusion Criteria

• Be willing and able to provide written informed consent for the trial.
• Be 18 years of age on day of signing informed consent.
• Have histologically-confirmed diagnosis of muscle-invasive T2-T4a, Nx or N0 urothelial cell carcinoma of the bladder. Subjects with tumors of mixed transitional/non-transitional cell histology are allowed, but transitional cell carcinoma must be the predominant histology (>50%). Subjects with predominant or exclusively non-transitional cell histology are not allowed.
• Must have undergone maximal transurethral resection of the bladder tumour, as is judged as safe as possible by the urologist performing the resection, within 42 days of treatment. Where patient has only had a biopsy/partial resection and is otherwise eligible for entry into the study, the case should be rediscussed with the referring urologist to see whether further resection would be feasible prior to embarking with the chemo-radiotherapy.
• Have elected not to undergo radical cystectomy, or are unsuitable for radical cystectomy.
• Planned for chemoradiotherapy as definitive treatment.
• Have a performance status of 0 or 1 on the ECOG Performance Scale
• Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of registering the patient on the trial.
• Absolute neutrophil count (ANC): ≥1.5 X 10^9/L
• Platelets: ≥100 X 10^9/L
• Hemoglobin: ≥9 g/dL without transfusion or EPO dependency
• Calculated creatinine clearance ≥50 mL/min
• Serum total bilirubin: ≤ 1.5 X ULN OR
• Direct bilirubin ≤ ULN for participants with total bilirubin levels: > 1.5 ULN
• AST and ALT: ≤ 2.5 X ULN
• Albumin: >25 g/dL
• International Normalized Ration (INR) or Prothrombin Time (PT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
• Activated Partial Thromboplastin Time (aPTT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
• Female participant of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registering the patient. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female participants of childbearing potential should be willing to use two methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
• Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Willing to consent to the use of their collected tumour specimen, blood and urine as detailed in the protocol for future scientific research including but not limited to DNA, RNA and protein based biomarker detection.

Exclusion Criteria

• Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) urothelial cell carcinoma of the urothelium. Patients who have involvement of the prostatic urethra with urothelial cell cancer (TCC) that was visibly completely resected and no evidence of stromal invasion of the prostate remain eligible.
• Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function.
• Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy.
• Bulky T3/T4a tumours unsuitable for curative treatment (i.e. >10 cms in any dimension); node positive disease
• Evidence of distant metastatic disease on CT chest/abdomen/pelvis performed within 42 days prior to study entry. Patients with pelvic lymph nodes deemed to be 'positive' are