Clinical trial NCT00445601: S0337, Gemcitabine After Surgery in Treating Patients With Newly Diagnosed or Recurrent Bladder Cancer
Official title: A Phase III Blinded Study of Immediate Post TURBT Instillation of Gemcitabine Versus Saline in Patients With Newly Diagnosed or Occasionally Recurring Grade I/II Superficial Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bladder Cancer
Keywords: transitional cell carcinoma of the bladder
stage 0 bladder cancer
stage I bladder cancer
recurrent bladder cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-03-09
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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 after surgery may kill more tumor cells. It is not yet known whether giving gemcitabine directly into the bladder is more effective than a placebo in treating bladder cancer.

PURPOSE: This randomized phase III trial is studying gemcitabine to see how well it works when given directly into the bladder compared with a placebo after surgery in treating patients with newly diagnosed or recurrent bladder cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the efficacy of a single intravesical instillation of gemcitabine hydrochloride vs placebo immediately after transurethral resection of the bladder tumor (TURBT) in preventing recurrence at 2 years in patients with grade 1 or 2 superficial transitional cell cancer of the bladder.

Secondary

* Compare whether a single instillation of intravesical gemcitabine hydrochloride can improve the time to progression to muscle invasive disease vs placebo in these patients.
* Compare the qualitative and quantitative toxicities of these regimens in these patients.
* Compare whether treatment with post-TURBT intravesical instillation of gemcitabine vs placebo results in reduced long-term morbidity in patients, as defined by requirement for fewer TURBTs, courses of traditional intravesical therapies, and surveillance cystoscopies over 4 years.

Tertiary

* Assess whether performing a combination of molecular and/or cytologic diagnostic marker tests, including NMP-22 Bladder Chek and BTA Stat every 3 months, can predict recurrence as accurately as cystoscopy alone in these patients.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to disease status (first occurrence vs recurrent disease) and number of tumor sites (1 vs ≥ 2). Patients are randomized to 1 of 2 treatment arms.

All patients undergo transurethral resection of the bladder tumor. Within 3 hours, patients receive intravesical therapy according to their randomized arm.

* Arm I: Patients receive intravesical gemcitabine hydrochloride over 1 hour.
* Arm II: Patients receive intravesical placebo over 1 hour. Urine is collected at baseline and then every 3 months for 2 years for research studies including the NMP-22 Bladder Chek and BTA Stat test.

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

PROJECTED ACCRUAL: A total of 340 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of newly diagnosed or recurrent transitional cell bladder cancer meeting the following criteria:

  * Ta or T1 primary tumor
  * Grade 1 or 2 disease
* No more than 2 recurrences (except for index tumor) within the 18 months prior to the index tumor's transurethral resection of the bladder tumor (TURBT)

  * Index tumor post-TURBT must meet the following criteria:

    * Ta or T1 tumor without any prior tumor in situ, grade 3 (high grade) disease within 2 years prior to index tumor TURBT, or invasion of the muscularis propria (stage ≥ T2)
    * Grade 1 or 2 disease (similar to papillary urothelial neoplasm of low malignant potential and low-grade bladder cancer)
* Not a candidate for a therapy other than TURBT (e.g., a series of instillations of intravesical immunotherapy \[e.g., BCG\] or intravesical chemotherapy, or cystectomy or partial cystectomy)
* Negative upper tract imaging studies within 1 year (365 days) prior to study entry

  * Imaging studies may be performed after registration provided it is done prior to TURBT on the day of treatment
* No urothelial cancer of the prostate or more distal urethra (or urethra at all in women) as assessed by endoscopy
* Must have a negative urine culture (less than or equal to 10,000 col/mL, mixed flora-likely contamination) OR negative urine analysis for infection AND negative nitrates on reagent strip, ≤ 10 white blood cell count (WBC)/high-power field, and no rods or organisms on examination of spun urine sediment OR an automated or visual reagent strip urinalysis that is negative for leukocytes and nitrates within the past 28 days
* TURBT planned within the next 28 days and planned treatment within 3 hours after TURBT

PATIENT CHARACTERISTICS:

* Zubrod performance status 0-1
* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other prior malignancy except for any of the following:

  * Adequately treated basal cell or squamous cell skin cancer
  * In situ cervical cancer
  * Adequately treated stage I or II cancer from which patient is in complete remission
  * Any other cancer from which patient has been disease-free for 3 years

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 145 days since prior intravesical therapy

Primary outcomes:
measure: Disease Recurrence Rate
timeFrame: Up to 2 Years
Secondary outcomes:
measure: Rate of Progression to Muscle Invasive Disease at 4 Years
timeFrame: 4 years
measure: Compare Qualitative and Quantitative Toxicities Between the Treatment Arms
timeFrame: Up to 4 years after Transurethral Resection of Bladder Tumor (TURBT)
measure: Rate of Disease Worsening Over 2 Years
timeFrame: Up to 2 years
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: Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Denver
country: United States
facility: Urology Center of Colorado
state: Colorado
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Lewiston
country: United States
facility: St. Joseph Regional Medical Center
state: Idaho
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Great Bend
country: United States
facility: St. Rose Ambulatory and Surgery Center
state: Kansas
city: Hays
country: United States
facility: Hays Medical Center
state: Kansas
city: Hutchinson
country: United States
facility: Hutchinson Hospital Corporation
state: Kansas
city: Kansas City
country: United States
facility: Kansas City Cancer Centers - West
state: Kansas
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Kansas City Cancer Centers - Southwest
state: Kansas
city: Pittsburg
country: United States
facility: Mount Carmel Regional Cancer Center
state: Kansas
city: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health Center
state: Kansas
city: Shawnee Mission
country: United States
facility: Kansas City Cancer Center - Shawnee Mission
state: Kansas
city: Topeka
country: United States
facility: St. Francis Comprehensive Cancer Center
state: Kansas
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: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Kansas City
country: United States
facility: Truman Medical Center - Hospital Hill
state: Missouri
city: Kansas City
country: United States
facility: Veterans Affairs Medical Center - Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Kansas City Cancer Centers - South
state: Missouri
city: Kansas City
country: United States
facility: Kansas City Cancer Centers - North
state: Missouri
city: Lee's Summit
country: United States
facility: Kansas City Cancer Centers - East
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
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: 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: 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: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
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: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Veterans Affairs Medical Center - Houston
state: Texas
city: Lackland Air Force Base
country: United States
facility: Wilford Hall Medical Center
state: Texas
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: Bellevue
country: United States
facility: Overlake Cancer Center at Overlake Hospital Medical Center
state: Washington
city: Centralia
country: United States
facility: Providence Centralia Hospital
state: Washington
city: Everett
country: United States
facility: Providence Regional Cancer Partnership
state: Washington
city: Federal Way
country: United States
facility: St. Francis Hospital
state: Washington
city: Olympia
country: United States
facility: Providence St. Peter Hospital Regional Cancer Center
state: Washington
city: Puyallup
country: United States
facility: Good Samaritan Cancer Center
state: Washington
city: Tacoma
country: United States
facility: Franciscan Cancer Center at St. Joseph Medical Center
state: Washington
city: Tacoma
country: United States
facility: Allenmore Hospital
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
city: Tacoma
country: United States
facility: MultiCare Regional Cancer Center at Tacoma General Hospital
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center - Tacoma
state: Washington
city: Tacoma
country: United States
facility: St. Clare Hospital
state: Washington
Study officials:
affiliation: James P. Wilmot Cancer Center
name: Edward M. Messing, MD, FACS
role: STUDY_CHAIR
affiliation: James P. Wilmot Cancer Center
name: Deepak M. Sahasrabudhe, MD
role: STUDY_CHAIR
affiliation: Oregon Health and Science University
name: Theresa M. Koppie, MD
role: STUDY_CHAIR
affiliation: Beaumont Physician Partners
name: David P. Wood, MD
role: STUDY_CHAIR
References:
citation: Messing EM, Tangen CM, Lerner SP, Sahasrabudhe DM, Koppie TM, Wood DP Jr, Mack PC, Svatek RS, Evans CP, Hafez KS, Culkin DJ, Brand TC, Karsh LI, Holzbeierlein JM, Wilson SS, Wu G, Plets M, Vogelzang NJ, Thompson IM Jr. Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial. JAMA. 2018 May 8;319(18):1880-1888. doi: 10.1001/jama.2018.4657.