Vefora, GETUG-AFU V06 study: Randomized multicenter phase II/III trial of fractionated cisplatin (CI)/gemcitabine (G) or carboplatin (CA)/g in patients (pts) with advanced urothelial cancer (UC) with impaired renal function (IRF)—Results of a planned interim analysis.

Abstract

461 Background: Standard treatment for advanced UC is chemotherapy (CT) combining CI and G. 70% of pts with UC are over 65 and 40% of them are unfit for CI because of IRF or comorbidities. CA replaces frequently CI, when creatinine clearance (Cr Cl) is < 60 ml/min according to Cockroft and Gault formula (CGF). However, CA tends to show a lower efficacy than CI, due to decreased dose intensity of CT. Methods: We performed a multicentre randomized phase II/III study in order to compare the activity and safety of a CT regimen with fractionated CI or CA for advanced UC in 1st line setting among pts unfit for standard CT because of IRF (40 ≤ Cr Cl ≤ 60ml/min) according to CGF. We report here the results of the interim analysis of phase II. Treatment: Arm A: CA AUC4,5 D1+ G 1000 mg/m² D1, [D1 = D21]; Arm B: fractionated CI 35 mg/m² D1D8 + G 1000 mg/m² D1D8, [D1 = D21] The co-primary objectives of the phase II were to evaluate activity (non-progression (RECIST V1.1) at (D21 C6)) and safety defined by the absence during treatment of: IRF: Cr Cl <35 mL/min or deterioration of Cr Cl >20%; delayed CT (≥ 2 weeks); decrease twice G dose on day 1 for: NCI CTC grade III or IV non-hematologic toxicity; hematologic toxicity; A two-stage Bryant and Day design was used. Results: A planned first step analysis was performed after randomization of 25 and 21 pts from April 2015 to January 2018. 23 and 19 of them were evaluable (resp. Arm A/B). 8 failures were reported for safety reason in experimental arm B, 7 for renal toxicity. Conclusions: According to our pre planned first step analysis, the trial met criteria for excessive toxicity in experimental arm (fractionated CI), predominantly renal toxicity. The study was therefore definitely stopped. Survival results will be available at the meeting. Clinical trial information: NCT02240017 . [Table: see text]