Pazopanib Hydrochloride in Treating Patients With Metastatic Urethral Cancer or Bladder Cancer That Has Relapsed or Not Responded to Treatment

Study Overview
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Brief Summary
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RATIONALE: Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well pazopanib hydrochloride works in treating patients with or metastatic urothelial cancer or bladder cancer that has relapsed or not responded to treatment.

Detailed Description
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OBJECTIVES: Primary To evaluate the activity of daily oral doses of pazopanib hydrochloride monotherapy in patients with relapsed/refractory metastatic urothelial carcinoma or transitional cell tumors. Secondary To evaluate the safety and tolerability of pazopanib hydrochloride monotherapy in a population of chemotherapy pretreated patients. To assess progression-free survival of these patients. Tertiary To evaluate the ability of whole-body 18FDG-PET to image metastases and monitor tumor response and to determine the rate of concordance with CT imaging and RECIST response criteria. To evaluate the relationship existing between tumor response measured by 18FDG-PET and progression-free survival. OUTLINE: This is a multicenter study. Patients receive oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo whole-body 18FDG-PET at baseline and periodically. After completion of study treatment, patients are followed for 2 years.

Official Title
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Phase 2 Study With the Multi-Targeted Tyrosine-Kinase Inhibitor Pazopanib (GW786034) for Patients With Relapsed or Refractory Urothelial Cancer

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: pazopanib hydrochloride
* Radiation: fludeoxyglucose F 18


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of transitional cell tumors of the bladder or the urothelium Metastatic disease Relapsed or refractory disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan Must have failed ≥ 1 cisplatin-based conventional chemotherapy regimen for metastatic disease (neoadjuvant/adjuvant therapy excluded) No history or clinical evidence of CNS metastases or leptomeningeal carcinomatosis, except for individuals who were previously treated for CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for the past 6 months PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy ≥ 12 weeks Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count ≥ 1,000/μL Platelet count ≥ 75,000/μL Total bilirubin ≤ 1.5 x upper limit of normal (ULN) ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement) Alkaline phosphatase ≤ 4 x ULN Serum creatinine ≤ 1.5 mg/dL PT-INR/PTT < 1.5 x ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 3 months after completion of study therapy Able to swallow oral medication None of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting Myocardial infarction Unstable angina Symptomatic peripheral vascular disease NYHA class III or IV congestive heart failure Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted) Uncontrolled hypertension No history of HIV infection or active chronic hepatitis B or C No active clinically serious infections > grade 2 NCI-CTC version 4.0 No seizure disorder requiring medication (e.g., steroids or anti-epileptics) No history of any of the following conditions within the past 6 months: Cerebrovascular accident Pulmonary embolism Untreated deep venous thrombosis No evidence or history of bleeding diathesis No known endobronchial lesions or involvement of large pulmonary vessels by tumor No hemoptysis within the past 6 weeks No gastrointestinal abnormalities that may increase the risk of GI bleeding or affect the absorption of investigational study drug No other cancer that is distinct in primary site or histology from the cancer being evaluated in this study, except cervical carcinoma in situ, treated basal cell carcinoma, or any cancer curatively treated > 5 years prior to study entry No substance abuse, medical, psychological, or social conditions that may interfere with the study participation or evaluation of the study results No concurrent unstable condition that could jeopardize patient safety and their compliance in the study No non-healing wound, fracture, or ulcer within the past 28 days No major trauma within the past 28 days No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib hydrochloride PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from all prior therapy At least 14 days since prior radiotherapy, except palliative radiotherapy At least 14 days since tumor embolization At least 14 days or 5 half-lives (whichever is longer) of a drug since prior chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal therapy At least 3 weeks since prior biologic response modifiers (e.g., G-CSF) G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity (e.g., febrile neutropenia) when clinically indicated or at the discretion of the investigator, however they may not be used to avoid a required dose reduction Chronic erythropoietin allowed provided no dose adjustment is undertaken within 2 months prior to the study or during the study No prior pazopanib hydrochloride No coronary artery by-pass graft surgery within the past 6 months No major surgery within the past 28 days Concurrent coumadin or heparin for therapeutic anticoagulation allowed provided that no prior evidence of underlying abnormality in PT-INR/PTT parameters exist Not concurrently undergoing renal dialysis

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: pazopanib hydrochloride|nan|
|Radiation: fludeoxyglucose F 18|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete and partial response) according to RECIST 1.1 criteria |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability, in terms of incidence, nature, and severity of treatment-related adverse events according to CTCAE v4.0 |  |  | 
| Progression-free survival |  |  | 

 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, recurrent urethral cancer, distal urethral cancer, proximal urethral cancer, urethral cancer associated with invasive bladder cancer, metastatic transitional cell cancer of the renal pelvis and ureter, recurrent transitional cell cancer of the renal pelvis and ureter, stage IV urethral cancer