Safety & Efficacy of Neoadjuvant Immunotherapy With Durvalumab (MEDI 4736) Combined With Neoadjuvant Chemotherapy (Gemcitabine/Cisplatin or Gemcitabine/Carboplatin) in Patients With Operable, High-risk, Localized Urothelial Carcinoma of the Upper Urinary Tract
Following radical nephrectomy (RNU) for upper tract urothelial carcinoma (UTUC) most patients face a poor prognosis. Indeed, patients who have undergone RNU for UTUC have 5-year recurrence-free and cancer specific survival probabilities of 69% and 73% respectively. The primary objective of this study is to assess the pathological complete response rate to combination therapy with neoadjuvant durvalumab and chemotherapy (Gemcitabine/Cisplatin) before surgery in patients with high-risk, localized, non-metastatic urothelial carcinomas of the upper tract.
• Patient has been correctly informed and has given signed consent.
• Patient is covered by a health insurance scheme.
• Patients aged over 70 must have a G8 score (Soubeyran et al. 2014) of at least 14.
• Patient's body weight must be over 30kg
• Patient has high-grade urothelial carcinoma of the renal pelvis or ureter confirmed histologically (uteroscopic biopsy) or cytologically (urine cytology).
• Presence of divergent histologies (i.e. squamous cell tumour, adenocarcinoma, small cell carcinoma, micropapillary variant) may also give rise to inclusion if there is a high prevalence (over 90%) of a urothelial component.
• Presence of EITHER high-grade disease on the uteroscopic tumor biopsy
• OR Presence of high-grade disease on urine cytology AND infiltrative aspect of renal pelvis/ ureteral wall on the CT scan (presence of hydronephrosis will be considered invasive by definition) with negative cystoscopy.
• Or in the absence of histological evidence, the opinion of the multidisciplinary consultation meeting (RCP) will prevail for the analysis of the imaging and the potential inclusion of the patient in the study
• No prior systemic therapies.
• ECOG performance status 0 to 1.
• M0 No or N1 disease on CT scan.
⁃ Required initial laboratory values :
• Absolute neutrophil count of over 1500 cells/mm²
• Platelet count of over 100,000 cells/mm3
• Hemoglobin over 9.0 g/dL
• Bilirubin below 1.5 times the Upper Limit of Normal for the institution
• Aspartase transaminase (ASAT) and Alanine transaminase (ALAT) below 2.5 x the Upper Limit of Normal for the institution.
• Alkaline phosphatase below 2.5 times the Upper Limit of Normal for the institution
• INR and aPTT below 1.5 times the Upper Limit of Normal for the institution.
• For Cohort 1 : An estimated glomerular filtration rate of over 60ml/min/1.73m² using the CKD-EPI and/or MDRD equation.
• For Cohort 2 : An estimated glomerular filtration rate of 40ml to 60ml/min/1.73m² using the CKD-EPI and/or MDRD equation.
• Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial.
• Patients must have a life expectancy of at least 12 weeks.