RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies such as BCG use different ways to stimulate the immune system and stop cancer cells from growing. It is not yet known whether AD 32 alone is more effective than AD 32 plus BCG following surgery for superficial bladder cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of AD 32 alone or with BCG following surgery in treating patients who have newly diagnosed or recurrent superficial bladder cancer.

Condition	Treatment or Intervention	Phase
stage I bladder cancer stage 0 bladder cancer recurrent bladder cancer	Procedure: chemotherapy  Procedure: surgery  Procedure: conventional surgery  Drug: AD 32  Drug: BCG	Phase II

OBJECTIVES: I. Evaluate the efficacy of peri-operative intravesical AD 32 alone or supplemented with BCG in patients with newly diagnosed or recurrent superficial bladder cancer characterized as either high risk or low risk based on the tumor markers p53 and pRb. II. For low risk patients, assess the efficacy of peri-operative AD 32 in preventing tumor recurrence. III. For high risk patients, assess the efficacy of combined intravesical therapy with AD 32 administered within 8 hours after transurethral resection along with BCG in decreasing the incidence of tumor progression. IV. Evaluate systemic exposure and urine recovery of AD 32 through pharmacokinetic analysis in a subset of patients.

PROTOCOL OUTLINE: This is a randomized, open label study. All patients undergo complete transurethral resection to remove bladder tumors. AD 32 is administered by catheter into the bladder within 8 hours after surgery. Patients must hold the AD 32 in the bladder for 90 minutes. Following pathological and tumor marker analysis, patients are assigned to the low or high risk group as defined by their p53 and pRb phenotype. Low risk patients with carcinoma in situ receive BCG by catheter into the bladder once weekly for 6 weeks beginning 7-21 days after treatment with AD 32. Patients assigned to the low risk group who do not have carcinoma in situ receive no further treatment. High risk patients also receive BCG once weekly for 6 weeks, and then once weekly for 3 weeks at 3 months, 6 months, and then every 6 months for a total of 3 years after the first BCG treatment. All patients undergo cystoscopy every 3 months for the first year, and then every 6 months for the next 2 years.

PROJECTED ACCRUAL: Approximately 200 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Newly diagnosed or recurrent (at least 2 occurrences within 12 months) Ta, multifocal Ta (at least 2 visible tumors), or stage T1 bladder cancer

• No carcinoma in situ (Tis) only
• No T2 or greater tumors

No evidence of upper tract (ureter or renal pelvic) transitional cell carcinoma based on intravenous pyelogram performed within 4 months of the TURB

--Prior/Concurrent Therapy--

Biologic therapy: No concurrent biological response modifiers

Chemotherapy: No other concurrent chemotherapy

Endocrine therapy: No concurrent hormonal therapy

Radiotherapy: No concurrent radiotherapy

Surgery: Not specified

--Patient Characteristics--

Age: 18 and over

Performance status: SWOG 0-2

Life expectancy: Not specified

Hematopoietic:

• WBC greater than 3,500/mm3
• Platelet count greater than 100,000/mm3

Hepatic: Not specified

Renal: Not specified

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or superficial transitional cell carcinoma of the bladder

Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States

Study chairs or principal investigators

Colin P. N. Dinney,  Study Chair,  Anthra Pharmaceuticals   

Study ID Numbers:  CDR0000066883; ANTHRA-A9701/ID97-038; MDA-ID-97038
Record last reviewed:  July 2003
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003759
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-14