Sunitinib in Treating Patients With Progressive Metastatic Transitional Cell Cancer of the Urothelium

Study Overview
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Brief Summary
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RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with progressive metastatic transitional cell cancer of the urothelium.

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with progressive metastatic transitional cell carcinoma of the urothelium treated with sunitinib malate. Determine the safety of this regimen in these patients. Secondary Determine the time to disease progression in patients treated with this regimen. To determine time to tumor progression (TTP) for sunitinib malate on a continuous dosing schedule for treatment of metastatic urothelial carcinoma. To estimate sunitinib and SU012662 trough plasma concentration (Ctrough) data for the continuous daily schedule and to determine potential association with efficacy and safety.

Official Title
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Phase II Study of Sunitinib in Metastatic Transitional Cell Carcinoma of the Urothelium

Conditions
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Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer

Intervention / Treatment
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* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma of the urothelium, including 1 of the following sites: Bladder Urethra Ureter Renal pelvis Progressive metastatic disease Progressive disease defined as new or progressive lesions on cross-sectional imaging Progressed despite prior treatment with cytotoxic chemotherapy Measurable disease Previously treated disease, as defined by the following: Received treatment with 1-4 cytotoxic agents Prior therapy must have included ≥ 1 of the following: Cisplatin Carboplatin Paclitaxel Docetaxel Gemcitabine hydrochloride Prior cytotoxic agents in the perioperative or metastatic setting allowed and may have been administered sequentially (e.g., first-line treatment followed by second-line treatment at time of progression) or all as part of a single regimen No symptomatic CNS metastases PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Absolute neutrophil count ≥ 1,000/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 8.0 g/dL Bilirubin ≤ 1.5 mg/dL (unless Gilbert's disease is present) AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver function abnormalities are due to underlying malignancy) Creatinine ≤ 2.0 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception None of the following within the past 6 months: Myocardial infarction Severe or unstable angina Coronary or peripheral artery bypass graft Symptomatic congestive heart failure Cerebrovascular accident or transient ischemic attack Pulmonary embolism No ongoing cardiac dysrhythmias ≥ grade 2 No prolonged QTc interval on baseline ECG No uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy No preexisting thyroid abnormality (i.e., thyroid function tests that cannot be maintained in the normal range with medication) No known HIV- or AIDS-related illness or other active infection PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 4 weeks since prior radiotherapy or chemotherapy At least 4 weeks since prior major surgery No other concurrent investigational drugs No concurrent participation in another clinical trial (supportive care trials or non-treatment trials [e.g., quality of life] allowed) No concurrent therapeutic doses of warfarin (low-dose warfarin ≤ 2 mg once daily for thromboembolic prophylaxis allowed)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunitinib<br>This is a phase II trial of Sunitinib in patients with metastatic urothelial carcinoma. Sunitinib will be administered at a dose of 50 mg orally once daily for four consecutive weeks followed by a two-week rest period for the initial population. A second cohort of patients will be enrolled, who will receive 37.5 mg of sunitinib orally, on a continuous dosing schedule. Intra-patient dose reduction may be required depending on the type and severity of individual toxicity encountered. Re-staging imaging studies will be performed after every cycle of treatment during the first 4 cycles and subsequently after every other cycle. Patients may continue on study as long as they are tolerating therapy and in the absence of disease progression. | Drug: sunitinib malate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Objective Response | Response rate as measured by RECIST criteria. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent bladder cancer, stage IV bladder cancer, transitional cell carcinoma of the bladder, anterior urethral cancer, posterior urethral cancer, recurrent urethral cancer, metastatic transitional cell cancer of the renal pelvis and ureter, recurrent transitional cell cancer of the renal pelvis and ureter, urethral cancer associated with invasive bladder cancer