806P - Phase II clinical and pharmacokinetic (PK) trial of zalypsis (Z) in patients with urothelial carcinoma (UC) progressing after a first-line platinum-...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Pharmacology
Urothelial Cancers
Presenter Joan Carles
Authors J. Carles1, J. Bellmunt2, P. Maroto3, A. Font4, R. Morales-Barrera1, C. Suarez1, C. Martin Lorente3, O. Etxaniz4, L. Capdevila4, D.E. Castellano5
  • 1Oncology, Hospital Vall d'Hebron, Barcelona/ES
  • 2Medical Oncology, University Hospital del Mar, 08003 - Barcelona/ES
  • 3Dept. Of Medical Oncology, Hospital de la Sta. Creu i St. Pau, ES-08025 - Barcelona/ES
  • 4Medical Oncology, Catalan Institute of Oncology ICO Badalona Hospital Germans Trias i Pujol, Medical Oncology, 08916 - Badalona/ES
  • 5Medical Oncology, Hospital Universitario 12 de Octubre, Madrid/ES

Abstract

Background

Platinum-based chemotherapy (CT) is beneficial as first-line treatment of advanced UC. However, the majority of patients develop recurrent disease with poor long-term survival rates[1]. Attempts to improve second-line treatments have evaluated single agents and multi-drug combinations, neither of which has managed to improve survival or achieve durable responses. Z is a cytotoxic agent that induces apoptosis by acting at cell cycle level, has DNA-binding properties and inhibits transcriptional responses. Z has shown anti-tumor activity in vitro and in vivo in xenograft models[2]. Based on the activity observed in a phase I study (1PR and 2 SD) in advanced bladder cancer we have designed a phase II study to explore the efficacy of Z in this setting.

Methods

Patients with histologically-confirmed advanced or metastatic UC, who had failed one prior line of platinum-based CT, with proven progression or relapse before study entry, were included. Patients were treated with a Z intravenous infusion of 3 mg/m2 over 1-hour and every 3 weeks. A two-stage design was chosen; at least four (of 17) evaluable patients had to reach the primary endpoint during the first stage in order to progress into a second stage of up to 37 patients. The primary endpoint was tumor control rate (TCR): percentage of patients with objective response (OR) of any duration or patients alive and progression-free (PFS) at three months.

Results

Twenty patients of a median age of 71 years (r: 54–83) were enrolled after a median of one prior treatment line (r:1–2). One patient was considered non-evaluable. No ORs were observed and only one patient had PFS ≥ 3 months. The median time on treatment was 1.68 months (r: 0.76–4.21). Toxicity consisted mostly of grade 1–2 fatigue, anorexia and nausea. Five patients had isolated troponin I increases (with no ECG or LVEF findings). Hematological toxicity was mild, one patient had grade 3 neutropenia and one patient had grade 3 thrombocytopenia.

Conclusion

Only one patient reached the primary endpoint (TCR) during the first stage; consequently, the study was closed and no further development was considered.

Disclosure

All authors have declared no conflicts of interest.