In this phase II study, eligible patients will be treated with maximal tumor resection and then started treatment within 8 weeks. Chemotherapy, Nivolumab and radiotherapy (RT) will be started on day one. Chemotherapy will be administered weekly during radiotherapy. Radiotherapy will be performed from Monday to Friday for five weeks. Nivolumab will be administered for one year (13 infusions).
Patients will have the complete tumour assessment by computed tomography scan (CT-scan) and cystoscopy up to 5 years after radiotherapy.
18 years old or older
Histologic diagnosis of predominantly urothelial carcinoma of the bladder. Focal differentiation allowed other than small cell histology.
Stage T2-T3 N0M0 (AJCC-TNM version 6) based on trans-urethral resection of bladder tumor (TURBT), CT or MRI imaging, +/- bimanual examination under anaesthesia.
FDG-PET within 6 weeks from the start of treatments, showing no evidence of lymph nodes or metastatic disease.
Prior systemic therapy for other urothelial tumours.
Prior RT to the pelvis
Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug, whichever is longer, prior to enrolment.
Patients with localized lower risk prostate cancer (defined as Stage ≤T2b, Gleason score ≤ 7, and PSA at prostate cancer diagnosis ≤ 20 ng/mL [if measured]) treated with radical prostatectomy and without prostate-specific antigen (PSA) recurrence are eligible.
Single group
Nivolumab
DrugThe recommended dose for nivolumab is 480 mg administered as 30 minutes IV infusions every 28 days for 13 infusions.
Nab paclitaxel
DrugThe recommended dose for nab-paclitaxel is 60 mg per square meter administered as 30 minutes IV infusions every 7 days (weekly), during the radiotherapy period.
Cisplatin
DrugThe recommended dose for cisplatin is 20 mg per square meter administered as 60 minutes IV infusions every 7 days (weekly), during the radiotherapy period.
Radiotherapy
RadiationRadiotherapy will be delivered over approximately 5 weeks.The total radiotherapy dose will be: 60 Gray in 25 fractions over 5 weeks on original bladder tumour, 50 Gray in 25 fractions over 5 weeks on whole bladder and pelvic nodes if included, administered as concomitant boost. Radiation therapy will be delivered once daily (Monday-Friday) continuously without a planned break for tumour response assessment during treatment.
Disease-free survival
Disease-free survival is defined as the rate of survival free of recurrence in pelvic nodes or bladder, or appearance of distant metastasis with data censored at the first sign of disease or second primary tumor, or death.
Rate of patients who require salvage cystectomy.
This is the number of patients over the total who had cystectomy after the end of study treatment.
Rate of locoregional Disease Free Survival.
This is the number of patients over the total who had no bladder or pelvic progression of disease.
Median Disease Free Survival.
This is defined as the time interval from the start of study treatment to the date of radiological or clinical progression or death due to any cause.
Overall survival
This is defined as the time interval from the start of study treatment to the date of death due to any cause.
Median Disease Free Survival by PD-L1 expression.
Patients with or without PD-L1 expression evaluated by Combined Positive Score (CPS) will be compared in terms of median disease free survival. Patients with CPS ≥ 10 will considered positive, the others negative.
Median Disease Free Survival by PI3KCA mutations
Patients with or without PI3KCA mutation will be compared in terms of median disease free survival.
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