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

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.

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