Open-label randomized multi-center phase 2 study: gemcitabine cisplatin plus avelumab or gemcitabine cisplatin as first-line treatment of patients with locally advanced or metastatic urothelial bladder carcinoma: GCisAve.

Abstract

BACKGROUND:

The standard treatment in first line of advanced or metastatic urothelial bladder cancer (MBC) is the association of Gemcitabine and Cisplatin (GC). Avelumab, an anti-PD-L1 agent, has recently demonstrated efficacy. The objective is to evaluate the combination of these 3 agents.

METHODS:

This phase II randomized open-label study, evaluated if GC-avelumab increases response rate and duration of response of patients in 1st line treatment for MBC compared to GC. Severe toxicities should not overlap and be acceptable. The two co-primary end points are the objective response rate and the incidence of severe toxicity after six cycles of treatment. The study will recruit 90 participants, randomized in two arms (1:2), GC (gemcitabine 1 000 mg/m2/j, J1,J8, Cisplatine 70 mg/m2, J1 = J21), and GC-avelumab (10 mg/Kg/3 semaines). Randomization will be stratified on Karnofsky status (≥ 80 % vs. < 80 %) and visceral vs non visceral metastases. The duration of the inclusion period is 24 months, with a duration of participation of each patient of 18 months and a total study duration of 42 months.

DISCUSSION:

If both efficacy and safety of the association of GC+avelumab are in the range of acceptable through this specific study design, this will support a subsequent randomized phase III study comparing both arms with an overall survival end-point. In addition, the evaluation of predictive parameters to be confirmed (e.g. the impact of tumor PD-L1 expression) or other immunological parameters, may support a selection of the population. NCT number : NCT03324282.

• Authors: Marine Gross-Goupil, Charlotte Domblides, Felix Lefort, Alain Ravaud
• Journal: Bulletin du cancer (Bull Cancer) Vol. 107 Issue 5S Pg. eS1-eS7 (Jun 2020) ISSN: 1769-6917 [Electronic] France
• PMID: 32620210 (Publication Type: Clinical Trial Protocol, Journal Article)
• Copyright: Copyright © 2020 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.

Chemical References

• Antibodies, Monoclonal, Humanized
• Deoxycytidine
• avelumab
• Cisplatin
• Gemcitabine

Topics

• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Carcinoma, Transitional Cell (drug therapy, pathology)
• Cisplatin (administration & dosage)
• Clinical Trials, Phase II as Topic (methods)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Humans
• Multicenter Studies as Topic (methods)
• Neoplasm Invasiveness
• Prospective Studies
• Randomized Controlled Trials as Topic (methods)
• Urinary Bladder Neoplasms (drug therapy, pathology)
• Gemcitabine