TOMBOLA

Treatment Of Metastatic Bladder cancer at the time Of biochemical reLApse following radical cystectomy - DaBlaCa-14

Aim: To investigate the response rate and oncological outcome of systemic immunotherapy administered at the time of biochemical relapse (ctDNA positive test) in Study Subjects who have undergone NAC followed by radical cystectomy because of MIBC. Long term survival of Study Subjects with positive ctDNA treated with immunotherapy will be compared to available historical data from clinical immunotherapy trials where Study Subjects are treated at the time of recurrence diagnosed by conventional CT routine follow-up.

The primary objective is complete response (CR) after treatment with investigational agent initiated by ctDNA positive status after radical cystectomy (with or without concomitant visible metastases on CT). Data will be compared to available historical data on response to PD-1 / PD-L1 targeted agents14,15. CR in the current study is defined as ctDNA negative status in the last plasma samples taken during IO treatment combined with negative imaging (CT) at the same time point after treatment. Thus, any metastasis visible on CT at the time of treatment initiation should undergo complete response. In Study Subjects without visible metastasis on CT at the time of treatment, initiation should result in unchanged status on CT.

Number of patients: 127. Study inclusion will continue until a total number of 127 Study Subjects have initiated treatment with the study drug Atezolizumab.

Method: The study will be conducted as a Single Country, Open-label, Single-arm, Non-randomized, Phase IV study where intervention is given based on an experimental design. Thus, blinding and randomization procedures are not applicable.

Study Subjects are included in the study at the time of indication for NAC followed by radical cystectomy, based on the histology with urothelial MIBC in the TURB specimen. Subtypes of urothelial carcinoma are all allowed. Surgery must be radical cystectomy with extended lymph node dissection to the aortic bifurcation and urinary diversion either by open or robotic assisted laparoscopic procedure.

Preoperative metastatic work-up should include FDG-PET/CT with no sign of distant metastasis.

Study Subjects are treated with conventional NAC prior to cystectomy if there are no contraindications for cisplatin (age > 75 years, GFR<60ml/min estimated by renal clearance (e.g. Chrome-EDTA-clearance or Tc-99m-DTPA-clearance)

In cases where NAC has been ceased after one dose of treatment due to adverse events or local non-metastatic progression, the protocol allows study subject to continue participation.

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