Clinical trial NCT00234039: S0353, Gemcitabine in Treating Patients With Recurrent Bladder Cancer That Has Not Responded to Previous Bacillus Calmette-Guerin
Official title: Phase II Study of Intravesical Gemcitabine in Patients With Superficial Bladder Cancer Who Have Progressed Despite Intravesical BCG
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: recurrent bladder cancer
stage 0 bladder cancer
stage I bladder cancer
transitional cell carcinoma of the bladder
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-10-06
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gemcitabine directly into the bladder may kill more tumor cells.

PURPOSE: This phase II trial is studying how well gemcitabine works in treating patients with recurrent bladder cancer that has progressed despite previous Bacillus Calmette-Guerin (BCG).

Detailed description: OBJECTIVES:

* Determine the 8-12 week efficacy of intravesical gemcitabine, in terms of complete response rate, in patients with recurrent superficial transitional cell carcinoma of the bladder that have progressed despite prior intravesical Bacillus Calmette-Guerin (BCG).
* Determine the recurrence-free, worsening-free, progression-free, and overall survival of patients treated with this drug.
* Evaluate the toxicity of this drug in these patients.
* Correlate, preliminarily, expression levels of genes or genetic polymorphisms involved in the gemcitabine pathway and angiogenesis with clinical toxicity, response, and relapse-free survival of patients treated with this drug.

OUTLINE: This is a multicenter study.

* Induction therapy: Patients receive gemcitabine intravesically once a week for 6 weeks (weeks 1-6) in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response proceed to maintenance therapy at week 14.
* Maintenance therapy: Patients receive gemcitabine intravesically once in weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 25-45 patients will be accrued for this study within 6-12 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed superficial transitional cell carcinoma (TCC) of the bladder meeting 1 of the following stage criteria:

  * Stage T1, grade 2-3
  * Stage Tis
  * Stage Ta, grade 3-4 or multifocal (\> 2 lesions)
* Must have received and failed ≥ 2 courses of intravesical Bacillus Calmette-Guerin (BCG) (one 6-week course, plus one 3-week course, or fewer weeks if BCG was discontinued due to side effects) within the past 3 years
* Recurrent disease

  * Must have had a transurethral resection of the bladder tumor (TURBT) or bladder biopsy within the past 60 days documenting tumor recurrence and tumor stage and grade

    * TURBT or biopsy must have been performed ≥ 6 weeks after the completion of BCG and/or other immunotherapy treatment (or ≥ 14 days after completion of intravesical chemotherapy treatment)
    * All visible tumor must have been resected at the time of the last biopsy
* No evidence of urethral or renal pelvis TCC by upper tract radiological imaging (e.g., intravenous pyelogram, CT urogram, or retrograde pyelogram) within the past 2 years

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Zubrod 0-2

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics
* Prior intravesical interferon alfa allowed, alone or in combination with Bacillus Calmette-Guerin (BCG)

Chemotherapy

* See Disease Characteristics
* No more than 1 course of intravesical chemotherapy (e.g., thiotepa, mitomycin, or doxorubicin) within the past year, defined as 6 or more weekly instillations, with or without monthly maintenance instillations
* No prior gemcitabine

Endocrine therapy

* Not specified

Radiotherapy

* No prior pelvic radiotherapy
* No concurrent radiotherapy to any other area of the body

Surgery

* See Disease Characteristics
* Recovered from prior surgery

Primary outcomes:
measure: Complete Response Rate at the End of Induction
timeFrame: Week 8-12, then every 3 months for the first 2 years, and then every 6 months for the years 3-5
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 1 year
measure: Recurrence-free Survival (RFS)
timeFrame: 1 year
measure: Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
timeFrame: Patients were assessed for adverse events weekly for 6 weeks and then every 4 weeks for 40 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Leesburg
country: United States
facility: Cancer Centers of Central Florida, PA
state: Florida
city: Aiea
country: United States
facility: Kapiolani Medical Center at Pali Momi
state: Hawaii
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Honolulu
country: United States
facility: OnCare Hawaii, Incorporated - Lusitana
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Cancer Institute at Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Straub Clinic and Hospital, Incorporated
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Medical Center - East
state: Hawaii
city: Honolulu
country: United States
facility: OnCare Hawaii, Incorporated - Kuakini
state: Hawaii
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Honolulu
country: United States
facility: Tripler Army Medical Center
state: Hawaii
city: Wailuku
country: United States
facility: Maui Memorial Medical Center
state: Hawaii
city: Wailuku
country: United States
facility: Pacific Cancer Institute - Maui
state: Hawaii
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Olathe
country: United States
facility: Olathe Cancer Center
state: Kansas
city: Shreveport
country: United States
facility: Highland Clinic
state: Louisiana
city: Shreveport
country: United States
facility: Feist-Weiller Cancer Center at Louisiana State University Health Sciences
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County Medical Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Muskegon
country: United States
facility: Mercy General Health Partners
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Great Falls
country: United States
state: Montana
city: Havre
country: United States
facility: Northern Montana Hospital
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology at KRMC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Coos Bay
country: United States
facility: Bay Area Hospital
state: Oregon
city: Portland
country: United States
facility: Knight Cancer Institute at Oregon Health and Science University
state: Oregon
city: Anderson
country: United States
facility: AnMed Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Knoxville
country: United States
facility: U.T. Medical Center Cancer Institute
state: Tennessee
city: San Antonio
country: United States
facility: Veterans Affairs Medical Center - San Antonio (Murphy)
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center
state: Texas
city: San Antonio
country: United States
facility: University Hospital - San Antonio
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Martinsville
country: United States
facility: Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County
state: Virginia
city: Bellingham
country: United States
facility: St. Joseph Cancer Center
state: Washington
city: Bremerton
country: United States
facility: Olympic Hematology and Oncology
state: Washington
city: Kennewick
country: United States
facility: Columbia Basin Hematology
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Minor and James Medical, PLLC
state: Washington
city: Seattle
country: United States
facility: Group Health Central Hospital
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: Polyclinic First Hill
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Casper
country: United States
facility: Rocky Mountain Oncology
state: Wyoming
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: University of Southern California
name: Eila C. Skinner, MD
role: STUDY_CHAIR
References: