A Phase I/II Single-Arm Trial to Evaluate the Combination of Cisplatin and Gemcitabine With the mTOR Inhibitor Temsirolimus for First-Line Treatment of Patients With Advanced Transitional Cell Carcinoma of the Urothelium
- To determine a safety profile of temsirolimus in combination with cisplatin and
gemcitabine hydrochloride, including dose-limiting toxicities (DLTs) and
maximum-tolerated dose (MTD) in patients with locally advanced and/or metastatic
transitional cell carcinoma of the urothelium. (phase I)
- To determine the recommended dose for the Phase II stage of the trial and subsequent
studies. (phase I)
- To assess progression-free survival (PFS) at six months from date of enrollment. (phase
- To determine the pharmacokinetic profile of temsirolimus in combination with cisplatin
and gemcitabine hydrochloride. (phase I)
- To determine tolerability (side-effects) and feasibility (number of participants
requiring dose delays or reduction and/or treatment withdrawal). (phase II)
- To determine objective response rate as assessed by RECIST. (phase II)
- To assess PFS of these patients. (phase II)
- To assess overall survival of these patients. (phase II)
- To determine toxicity during and after treatment in these patients. (phase II)
OUTLINE: This is a multicenter, phase I dose-escalation study of temsirolimus followed by a
phase II study.
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, cisplatin IV
over 3-4 hours on day 1, and temsirolimus IV over 30 minutes on days 1 or 2, 8 or 9, and 15.
Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or
Blood specimens may be collected periodically for pharmacokinetic studies.
After completion of study treatment, patients are followed at 6 months and 1 year.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
Masking: Open Label, Primary Purpose: Treatment
Safety (recommended phase II dose and dose-limiting toxicities) (phase I)
Leeds Cancer Centre at St. James's University Hospital