A Phase II Study of R115777 (Zarnestra) in Superficial Transitional Cell Carcinoma of Bladder

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed transitional cell carcinoma (TCC) of the bladder with or
without associated carcinoma in situ

- Stage 0 or I (Ta or T1)

- Grade 1, 2, or 3 TCC

- Cystoscopically and histologically confirmed recurrent disease after at least 1
course of standard first-line intravesical therapy (e.g., BCG or mitomycin) within
the past 12 months

- Complete transurethral resection of bladder tumor performed within past 4 weeks

- Rendered clinically and cystoscopically tumor free

- Negative cytology

- No upper tract TCC by intravenous pyelogram, retrograde pyelogram, or CT scan of
kidneys (with contrast)

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2 OR

- Karnofsky 60-100%

Life expectancy

- More than 1 year

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 normal

- AST/ALT no greater than 2.5 times upper limit of normal (ULN)

Renal

- Creatinine no greater than 1.25 times ULN OR

- Creatinine clearance at least 60 mL/min

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- No uncontrolled hypertension

Other

- Able to swallow and retain oral medication

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior allergic reactions to compounds of similar chemical or biological
composition to study drug (e.g., other imidazoles such as ketoconazole and other
imidazole-based antifungal agents, losartan, metronidazole, or cimetidine)

- No other prior or concurrent malignancy within the past 5 years except
nonmelanomatous skin cancer

- No other uncontrolled concurrent illness that would preclude study participation

- No ongoing or active infection

- No active peptic ulcer disease

- No psychiatric illness or social situation that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- See Disease Characteristics

- No prior systemic chemotherapy for bladder cancer

Endocrine therapy

- Not specified

Radiotherapy

- No prior radiotherapy for bladder cancer

Surgery

- See Disease Characteristics

Other

- No single-dose post-transurethral resection (TUR) adjuvant intravesical therapy
(after TUR that is performed immediately preceding study entry)

- At least 4 weeks since prior investigational agents

- No concurrent commercial or other investigational agents or therapies for malignancy

- No other concurrent therapy for bladder cancer

- No concurrent combination anti-retroviral therapy for HIV-positive patients