Bortezomib in Treating Patients With Advanced or Metastatic Transitional Cell Cancer of the Bladder, Renal Pelvis, or Ureter

Study Overview
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Brief Summary
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RATIONALE: Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: This phase II trial is studying how well bortezomib works in treating patients with advanced or metastatic transitional cell cancer of the bladder, renal pelvis, or ureter.

Detailed Description
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OBJECTIVES: Determine the response rate and duration of response in patients with advanced or metastatic transitional cell cancer of the bladder, renal pelvis, or ureter when treated with bortezomib. Determine the 1-year, median, and overall survival rate of patients treated with this drug. Determine the stable disease rate and duration and time to progression in patients treated with this drug. Determine the toxicity of this drug in these patients. Correlate baseline and post-treatment levels of NF-kappaB and HIF-1 alpha in tumor biopsies with clinical outcome in patients treated with this drug. OUTLINE: This is a nonrandomized, open-label, multicenter study. Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients in complete remission (CR) may receive up to 2 courses after confirmation of CR. Patients are followed within 3 weeks and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 20-35 patients will be accrued for this study within approximately 6.6-17.5 months.

Official Title
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A Phase II Study of PS-341 in Advanced or Metastatic Urothelial Cancer (Transitional Cell Cancer of the Bladder, Ureter, and Renal Pelvis)

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

Intervention / Treatment
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* Drug: bortezomib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed transitional cell cancer of the urothelium, including the bladder, renal pelvis, or ureter Advanced or metastatic disease At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan The following are not considered measurable disease: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 OR Karnofsky 80-100% Life expectancy More than 3 months Hematopoietic WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 1.25 times upper limit of normal (ULN) AST/ALT no greater than 3 times ULN (less than 5 times ULN if liver metastases are present) Renal Creatinine no greater than 1.5 times ULN OR Creatinine clearance at least 45 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able and willing to undergo biopsy of tumor lesions No other primary cancer requiring treatment within the past 3 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix No grade 1 or greater peripheral neuropathy No ongoing or active infection No other concurrent uncontrolled illness No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No more than 2 prior chemotherapy regimen for metastatic disease Prior neoadjuvant or adjuvant therapy allowed provided it was completed more than 12 months prior to study entry Patients who relapse within 12 months after completion of neoadjuvant or adjuvant therapy are allowed provided they did not receive chemotherapy for recurrent disease More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Prior chemotherapy as a radiosensitizer is allowed* NOTE: *May be administered concurrently with radiotherapy; may be in addition to a single line of therapy for locally advanced or metastatic disease Endocrine therapy Not specified Radiotherapy See Chemotherapy More than 4 weeks since prior myelotoxic radiotherapy (more than 3,000 cGy to fields including substantial bone marrow) and recovered No concurrent radiotherapy Surgery At least 4 weeks since prior surgery for cancer of the urothelium (except nephrostomy tubes and ureteral stents) Other At least 4 weeks since any prior therapy and recovered No other concurrent investigational or commercial agents or therapies intended to treat the malignancy No concurrent combination antiretroviral therapy for HIV-positive patients

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bortezomib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response by RECIST criteria every 6 weeks |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response duration |  |  | 
| Stable disease duration |  |  | 
| Progression-free survival |  |  | 
| Overall survival |  |  | 
| Toxicity |  |  | 

 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, metastatic transitional cell cancer of the renal pelvis and ureter, recurrent transitional cell cancer of the renal pelvis and ureter, regional transitional cell cancer of the renal pelvis and ureter, transitional cell carcinoma of the bladder