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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00066352
First received: August 6, 2003
Last updated: July 23, 2008
Last verified: November 2005
  Purpose

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 Intervention Phase
Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Masking: 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response by RECIST criteria every 6 weeks [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response duration [ Designated as safety issue: No ]
  • Stable disease duration [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Study Start Date: September 2003
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066352

Locations
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
CCOP - Evanston
Evanston, Illinois, United States, 60201
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153-5500
Oncology/Hematology Associates of Central Illinois, P.C.
Peoria, Illinois, United States, 61615-7828
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 62701
United States, Indiana
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States, 46885-5099
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
United States, Michigan
Oncology Care Associates, P.L.L.C.
Saint Joseph, Michigan, United States, 49085
United States, Wisconsin
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, Canada, K1H 8L6
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Princess Margaret Hospital, Canada
Investigators
Study Chair: Eric Winquist, MD London Regional Cancer Program at London Health Sciences Centre
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00066352     History of Changes
Other Study ID Numbers: CDR0000315537, PMH-PHL-018, NCI-6150
Study First Received: August 6, 2003
Last Updated: July 23, 2008
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Diseases
Ureteral Diseases
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014