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

Bladder Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00066352
• Other study ID #: PMH-PHL-018
• Secondary ID: CDR0000315537NCI
• Status: Completed
• Phase: Phase 2
• First received: August 6, 2003
• Last updated: July 22, 2015
• Start date: September 2003

Study information

• Verified date: July 2015
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: September 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Transitional Cell Cancer of the Renal Pelvis and Ureter
• Ureteral Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• bortezomib

Locations

Country	Name	City	State
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	CCOP - Evanston	Evanston	Illinois
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Oncology/Hematology Associates of Central Illinois, P.C.	Peoria	Illinois
United States	Oncology Care Associates, P.L.L.C.	Saint Joseph	Michigan
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response by RECIST criteria every 6 weeks			No
Secondary	Objective response duration			No
Secondary	Stable disease duration			No
Secondary	Progression-free survival			No
Secondary	Overall survival			No
Secondary	Toxicity			Yes