S0337, Gemcitabine After Surgery in Treating Patients With Newly Diagnosed or Recurrent Bladder Cancer

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00445601
• Other study ID #: CDR0000534235
• Secondary ID: S0337U10CA032102
• Status: Completed
• Phase: Phase 3
• Start date: September 2007
• Est. completion date: June 2017

Study information

• Verified date: January 2020
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 406
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• gemcitabine hydrochloride
Given intravesically

Other:
• placebo
Given intravesically

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	Overlake Cancer Center at Overlake Hospital Medical Center	Bellevue	Washington
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Providence Centralia Hospital	Centralia	Washington
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Urology Center of Colorado	Denver	Colorado
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	St. Francis Hospital	Federal Way	Washington
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	St. Rose Ambulatory and Surgery Center	Great Bend	Kansas
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Northern Montana Hospital	Havre	Montana
United States	Hays Medical Center	Hays	Kansas
United States	St. Peter's Hospital	Helena	Montana
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	Veterans Affairs Medical Center - Houston	Houston	Texas
United States	Hutchinson Hospital Corporation	Hutchinson	Kansas
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kansas City Cancer Centers - North	Kansas City	Missouri
United States	Kansas City Cancer Centers - South	Kansas City	Missouri
United States	Kansas City Cancer Centers - West	Kansas City	Kansas
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Truman Medical Center - Hospital Hill	Kansas City	Missouri
United States	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri
United States	Wilford Hall Medical Center	Lackland Air Force Base	Texas
United States	Kansas City Cancer Centers - East	Lee's Summit	Missouri
United States	St. Joseph Regional Medical Center	Lewiston	Idaho
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Providence St. Peter Hospital Regional Cancer Center	Olympia	Washington
United States	Kansas City Cancer Centers - Southwest	Overland Park	Kansas
United States	Mount Carmel Regional Cancer Center	Pittsburg	Kansas
United States	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Good Samaritan Cancer Center	Puyallup	Washington
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	University of California Davis Cancer Center	Sacramento	California
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	Cancer Therapy and Research Center	San Antonio	Texas
United States	University Hospital - San Antonio	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	Kansas City Cancer Center - Shawnee Mission	Shawnee Mission	Kansas
United States	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana
United States	Allenmore Hospital	Tacoma	Washington
United States	CCOP - Northwest	Tacoma	Washington
United States	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington
United States	Madigan Army Medical Center - Tacoma	Tacoma	Washington
United States	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington
United States	St. Clare Hospital	Tacoma	Washington
United States	St. Francis Comprehensive Cancer Center	Topeka	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Recurrence Rate	Percentage of patients who experienced a recurrence of grade 1 or 2 superficial transitional cell cancer of the bladder between the date of registration and 24 months. Disease recurrence considered to occur at date of first observation of recurrent disease subsequently confirmed by biopsy. Patients without recurrence were censored at the time of their last cystoscopy.	Up to 2 Years
Secondary	Rate of Progression to Muscle Invasive Disease at 4 Years	From date of registration to date of diagnosis of progressive disease. Censor at date of last disease assessment for those without progression.	4 years
Secondary	Compare Qualitative and Quantitative Toxicities Between the Treatment Arms	Number of patients with Grade 3 through Grade 5 adverse events that are related to study drug	Up to 4 years after Transurethral Resection of Bladder Tumor (TURBT)
Secondary	Rate of Disease Worsening Over 2 Years	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.	Up to 2 years

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive