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

• Status: Completed
• Trial end date: 2016-03-16
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cardiff University; Wales Cancer Trials Unit
• Treatments: Cisplatin; Everolimus; Gemcitabine; Sirolimus

Criteria

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