Gemcitabine Hydrochloride, Cisplatin, and Sunitinib Malate as First-Line Therapy in Treating Patients With Locally Advanced And/or Metastatic Transitional Cell Carcinoma of the Urothelium (SUCCINCT)

OBJECTIVES:

• To determine the activity, safety, and feasibility of gemcitabine hydrochloride and cisplatin in combination with sunitinib malate as first-line therapy in patients with locally advanced and/or metastatic transitional carcinoma of the urothelium.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, cisplatin IV over 3-4 hours on day 1, and oral sunitinib malate once daily on days 2-15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 6 months and 1 year.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma of the urothelium

• Pure or mixed histology
• Upper or lower urinary tract
• Radiologically measurable, locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy meeting 1 of the following criteria:

• T4b (bladder) or T4 (renal pelvis/ureter), any N, any M
• Any T, N2-3, any M
• Any T, any N, M1
• No urothelial 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
• GFR ≥ 60 mL/min (uncorrected for surface area and measured by isotopic means)
• PT or INR ≤ 1.5 times ULN
• 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 uncontrolled hypertension
• No symptomatic coronary artery disease, myocardial infarction within the past 6 months, congestive cardiac failure (NYHA class III-IV disease), or uncontrolled or symptomatic cardiac arrhythmia
• No clinically significant bacterial or fungal infection
• No concurrent grapefruit juice

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 that have known adverse interactions with sunitinib malate (i.e., strong CYP3A4 inhibitors or inducers)
• No prior or concurrent live vaccines (e.g., measles, mumps, rubella, oral polio, bacille Calmette-Guérin [BCG], yellow fever, varicella, and TY21a typhoid vaccines)