JaNEO – A phase Ib/II study assessing the neo-adjuvant combination therapy of vinflunine (VFL) with cisplatin (CDDP) followed by radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC)

Background

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.

Trial design

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

EudraCT 2016-000081-33

Legal entity responsible for the study

Ligartis GmbH

Funding

Pierre Fabre GmbH

Disclosure

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.