Neo-adjuvant chemotherapy (CTx) prior to RC leads to a significant improvement in 5-year survival in MIBC. Guidelines recommend CDDP-based CTx. However, the optimal regimen is still controversial and no standard has been defined so far. VFL, as a single agent, has proven clinical activity in urothelial carcinoma. VFL and CDDP mediate complementary mechanisms of action and their combination may provide a relevant benefit in the neoadjuvant setting.
Systemically untreated patients with MIBC, clinically staged as T2-T4a (cN0, cM0) and with an ECOG performance status of 0-1 will be enrolled in this national, multi-center, prospective, open, single-arm Phase Ib/II trial. Study treatment consists of 4 cycles (q3w) of VFL (280mg/m2) and CDDP (70mg/m2), followed by RC within 4 weeks after CTx. In the phase Ib part of the study, a 3 + 6 patient safety cohort will be treated first to prove safety of the combination. Occurrence of ≥2 unacceptable toxicities (UT) or any grade 5 event will lead to discontinuation within the first cohort (3 patients), as well ≥4 UTs or any grade 5 event within the complete safety period (consisting of the 3 + 6 patients). Following this safety period, up to a total of 36 evaluable patients will be recruited into the phase II part of the trial in the frame of a Simon-two-stage design. Pathological tumor response based on central pathology review is the primary endpoint. The null hypothesis, which is the defined as a true response rate of 25%, will be tested against a one-sided alternative. In the first stage, 17 patients will be accrued. If there are ≥5 responses in these 17 patients, the study will be continued to full recruitment to a total of 36 patients. The null hypothesis will be rejected if ≥14 responses are observed in 36 patients, with a type I error rate of 0.05 (one-sided) and a power of 0.8 when the true response rate is 45%. Further endpoints are the rate of radiological response and progression (RECIST 1.1), cancer-specific survival, quality of life and safety. A translational research program aiming at the identification of predictive biomarkers will accompany this clinical trial.
Clinical trial identification
Legal entity responsible for the study
Pierre Fabre GmbH
A. Hegele, G. Gakis: Pierre Fabre: Advisory Role, Honoraria, Research Funding C-H. Ohlmann: Pierre Fabre: Advisory Role, Honoraria. All other authors have declared no conflicts of interest.