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

Sponsor

University Health Network, Toronto (Other)

Overall Status

Completed

CT.gov ID

NCT00066352

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter	Drug: bortezomib	Phase 2

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Sep 1, 2003

Actual Primary Completion Date :

Sep 1, 2003

Outcome Measures

Primary Outcome Measures

Objective response by RECIST criteria every 6 weeks []

Secondary Outcome Measures

Objective response duration []
Stable disease duration []
Progression-free survival []
Overall survival []
Toxicity []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
2	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
3	CCOP - Evanston	Evanston	Illinois	United States	60201
4	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
5	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153-5500
6	Oncology/Hematology Associates of Central Illinois, P.C.	Peoria	Illinois	United States	61615-7828
7	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62701
8	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46885-5099
9	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
10	Oncology Care Associates, P.L.L.C.	Saint Joseph	Michigan	United States	49085
11	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
12	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
13	London Regional Cancer Program at London Health Sciences Centre	London	Ontario	Canada	N6A 4L6
14	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario	Canada	K1H 8L6
15	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9