Neoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL)

Inclusion criteria

• Newly diagnosed radiographically visible (CT or MRI) cT1-4 N0 M0 with positive selective urinary cytology, positive bladder urinary cytology, or endoscopic biopsy for high grade urothelial cell carcinoma
• Age ≥18 years of age
• Eastern Cooperative Oncology Group (ECOG) score 0-1
• Medically appropriate candidate for radical nephroureterectomy or ureterectomy as per participating site attending urologic oncologist
• Medically appropriate candidate for cisplatin-based chemotherapy as per participating site attending medical oncologist
• Adequate organ system function defined as follows: absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,00/mm3, hemoglobin ≥ 90 g/L, ALT and AST < 2.5 x upper limit of normal, electrolytes (Na, K, Mg, Ca): within normal limits, GFR ≥ 60 mL/min

Patients who are randomized to the adjuvant chemotherapy will be reassessed for suitability to receive adjuvant chemotherapy after definitive surgery (nephroureterectomy or ureterectomy) based on the following criteria:

• pT2-4 N0-3 M0 or pT any N1-3 M0 with predominant urothelial component
• ECOG score 0-2
• Medically appropriate candidate for platin-based chemotherapy as per participating site attending medical oncologist
• Adequate organ system function defined as follows: absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,00/mm3, hemoglobin ≥ 90 g/L, ALT and AST < 2.5 x upper limit of normal, electrolytes (Na, K, Mg, Ca): within normal limits, GFR ≥ 30 mL/min

Exclusion criteria

• Metastatic disease
• Radiographically visible nodal disease
• Concurrent muscle-invasive bladder cancer (non-muscle invasive bladder cancer is acceptable)
• Solitary kidney
• Other cancer diagnosis or systemic chemotherapy use within 2 years of study enrollment (prior bladder cancer and intravesical therapy allowed)
• Concomitant diseases that are a formal exclusion to cisplatin chemotherapy (deafness, ≥ grade II neuropathy, serious active infection)
• Concomitant use of any other investigational drugs
• Pregnancy or breast feeding (you must remain on contraception, not father a child or donate sperm while receiving gemcitabine/cisplatin and for 6 months following the last dose)