Gemcitabine Hydrochloride, Cisplatin, and Temsirolimus as First-Line Therapy in Treating Patients With Locally Advanced and/or Metastatic Transitional Cell Cancer of the Urothelium

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma of the urothelium

  • Pure or mixed histology
  • Upper or lower urinary tract

• Radiologically evaluable* locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy, meeting any 1 of the following criteria:

  • T4b, any N, any M
  • Any T, N2-3, any M
  • Any T, any N, M1
• NOTE: *Patients enrolled in the phase II portion of the trial must have radiologically measurable disease.
• No transitional cell cancer for which subsequent radical treatment is being considered with a view to possibly cure the disease
• No history of CNS metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Life expectancy ≥ 3 months
• Absolute neutrophil count ≥ 1.5 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and ALP ≤ 2.5 times ULN
• PT or INR ≤ 1.5
• GFR ≥ 60 mL/min (uncorrected for surface area and measured by isotopic means)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Fit to receive cisplatin-containing combination chemotherapy
• No previous malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or incidental localized prostate cancer
• No known HIV positivity or chronic hepatitis B or C infection
• No symptomatic coronary artery disease, myocardial infarction within the past 6 months, congestive cardiac failure (NYHA class III or IV disease), or uncontrolled or symptomatic cardiac arrhythmia
• No clinically significant bacterial or fungal infection

PRIOR CONCURRENT THERAPY:

• At least 1 month since prior radiotherapy or radiotherapy involving more than 30% of total bone marrow volume
• At least 1 month since prior investigational drug

• No prior systemic therapy for locally advanced or metastatic disease

  • Patients who have received prior neoadjuvant or adjuvant chemotherapy for urothelial cancer (up to 4 courses), completed at least 6 months prior to first documented disease progression are eligible

• No concurrent anticoagulant therapy with warfarin or unfractionated heparin

  • Patients requiring anticoagulation may be entered on study after successful conversion to low molecular weight heparin
• No concurrent medications which have known adverse interactions with the treatment used on this trial (e.g., CYP3A4 inhibitors or inducers in phase I of this trial)
• No prior or concurrent live vaccines (e.g., measles, mumps, rubella, oral polio, Bacille Calmette-Guérin [BCG], yellow fever, varicella, and TY21a typhoid vaccines)
• No concurrent grapefruit juice