Clinical trial NCT00066352: Bortezomib in Treating Patients With Advanced or Metastatic Transitional Cell Cancer of the Bladder, Renal Pelvis, or Ureter
Official title: A Phase II Study of PS-341 in Advanced or Metastatic Urothelial Cancer (Transitional Cell Cancer of the Bladder, Ureter, and Renal Pelvis)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Keywords: 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
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-08-07
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective response by RECIST criteria every 6 weeks
Secondary outcomes:
measure: Objective response duration
measure: Stable disease duration
measure: Progression-free survival
measure: Overall survival
measure: Toxicity
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Harvey
country: United States
facility: Ingalls Cancer Care Center at Ingalls Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Oncology/Hematology Associates of Central Illinois, P.C.
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Saint Joseph
country: United States
facility: Oncology Care Associates, P.L.L.C.
state: Michigan
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: London Health Sciences Centre
name: Eric Winquist, MD
role: STUDY_CHAIR
References:
citation: Gomez-Abuin G, Winquist E, Stadler WM, Pond G, Degendorfer P, Wright J, Moore MJ. A phase II study of PS-341 (Bortezomib) in advanced or metastatic urothelial cancer. A trial of the Princess Margaret Hospital and University of Chicago phase II consortia. Invest New Drugs. 2007 Apr;25(2):181-5. doi: 10.1007/s10637-006-9009-4. Epub 2006 Sep 16.