Gemcitabine Hydrochloride, Cisplatin, and Temsirolimus as First-Line Therapy in Treating Patients With Locally Advanced and/or Metastatic Transitional Cell Cancer of the Urothelium
Condition: Bladder Cancer; Transitional Cell Cancer of the Renal Pelvis and Ureter; Urethral Cancer
MeSH terms: Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urethral Neoplasms; Kidney Neoplasms; Ureteral Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work
      in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. Temsirolimus may stop the growth of tumor cells by blocking some
      of the enzymes needed for cell growth. Giving gemcitabine hydrochloride and cisplatin
      together with temsirolimus may kill more tumor cells.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus
      given together with gemcitabine hydrochloride and cisplatin as first-line therapy in treating
      patients with locally advanced and/or metastatic transitional cell cancer of the urothelium.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  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
           II)

      Secondary

        -  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
      unacceptable toxicity.

      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
    

Intervention name(s): cisplatin; gemcitabine hydrochloride; temsirolimus; pharmacological study
Intervention type(s): Drug; Drug; Drug; Other
Intervention MeSH terms: Sirolimus; Gemcitabine; Temsirolimus; MTOR Inhibitors
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: transitional cell carcinoma of the bladder; recurrent bladder cancer; recurrent urethral cancer; recurrent transitional cell cancer of the renal pelvis and ureter; stage IV bladder cancer; metastatic transitional cell cancer of the renal pelvis and ureter; regional transitional cell cancer of the renal pelvis and ureter; distal urethral cancer; proximal urethral cancer; urethral cancer associated with invasive bladder cancer; stage IV urethral cancer