873TiP - A phase 2 study of paclitaxel and ifosfamide plus either cisplatin or carboplatin for patients with metastatic non-transitional cell carcinoma of t...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Urothelial Cancers
Presenter Patrizia Giannatempo
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors P. Giannatempo1, D. Magazzù2, D. Raggi3, E. Farè3, M. Marongiu3, E. Coradeschi2, N. Nicolai4, L. Piva5, M. Catanzaro5, D. Biasoni5, T. Torelli5, M. Maffezzini5, S. Stagni5, P. Valagussa6, R. Salvioni4, A. Necchi3
  • 1Dept. Genitourinary, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 2Dept. Statistics, Fondazione Michelangelo, 20154 - Milan/IT
  • 3Medical Oncology/urology Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 4Surgery Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 5Surgery - Urology Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 6Clinical Research, Fondazione Michelangelo, 20154 - Milano/IT

Abstract

Background

Transitional cell carcinoma (TCC) is the most common histology accounting for 90% of cases, and the remaining 10% are represented by pure divergent histologies (non-TCCs) such as small cell and squamous cell carcinoma, adenocarcinoma, and micropapillary variant. All non-TCCs are associated with features of aggressiveness such as advanced tumor stage, high risk of recurrence and cancer specific mortality compare to TCC. No standard of care for non-TCCs has been established. The primary objective will be to determine the activity of the combination of paclitaxel, ifosfamide, and cisplatin (TIP) (or carboplatin) in patients with non-TCCs. Secondary objectives will include safety and survival.

Trial design

66 pts with locally advanced (i.e. T3b-4 ± N+) or metastatic non-TCCs will receive paclitaxel 175 mg/m2 on day 1, and ifosfamide 1200 mg/ m2 + cisplatin 25 mg/ m2 on days 1-3 (or carboplatin AUC 4.5 on day 1) every 21 days for 6 cycles. Further eligibility requirements will include ECOG-PS ≤ 1 and no prior systemic therapy, except for relapse after >6 months of perioperative treatment. Carboplatin will be administered instead of cisplatin for patients who will be judged as cisplatin-ineligible (Galsky MD, Lancet Oncol 2011). Patients will be staged and evaluated every 2 cycles with computed tomography (CT) and positron emission tomography (PET)/CT scans. The primary endpoint is progression-free survival (PFS). Simon's Optimal 2-stage design is applied. The null hypothesis that the PFS rate at 6 months is ≤ 40% will be tested against a one-sided alternative that the 6-month PFS rate is ≥ 57%. Based on a nominal power of 80% and alpha (one-sided) of 5%, in the first stage 19 patients will be accrued. If there will be ≤ 8 progression-free patients at 6 months, the study will be stopped. Otherwise 47 additional patients will be accrued for a total of 66. The null hypothesis will be rejected if ≥ 33 patients will be progression free at 6 months. This design yields a type I error rate of 4.9% and power of 80.3% when the PFS rate at 6 months is 57%. At present, one patient has been enrolled and is under treatment. The trial is sponsored by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano Italy (EudraCT registry number 2014-000043-32).

Disclosure

All authors have declared no conflicts of interest.