RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of chemotherapy in treating patients with early-stage bladder cancer that has not responded to BCG therapy.

Condition	Treatment or Intervention	Phase
transitional cell carcinoma of the bladder stage I bladder cancer stage 0 bladder cancer	Procedure: chemotherapy  Drug: AD 32	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the recurrence rate and disease free survival in patients with recurrent or refractory papillary transitional cell carcinoma of the bladder with or without carcinoma in situ of the bladder treated with intravesical AD 32. II. Evaluate the safety of administering this drug in these patients. III. Determine the effectiveness of this drug, in terms of recurrence rates and disease free survival, in these patients.

PROTOCOL OUTLINE: Patients are stratified according to cellular diagnosis (papillary transitional cell carcinoma (Ta/T1) with no carcinoma in situ (Tis) vs Tis with or without Ta/T1). Patients receive intravesical AD 32 once a week for 6 weeks. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically confirmed recurrent superficial bladder cancer defined as papillary transitional cell carcinoma (stage Ta/T1) and/or carcinoma in situ (stage Tis) of the urinary bladder

• No evidence of invasion of the underlying muscle (stage T2) at baseline

Must meet 1 of the following criteria:

• Failure of at least 2 prior courses of intravesical therapy, 1 of which must have been a course of BCG OR
• Recurrent or persistent disease within 6 months after failing a 6-week course of BCG followed by maintenance therapy OR
• Inability or ineligibility to complete 1 course of intravesical therapy with BCG, and failure of 2 prior courses of intravesical therapy with an alternative agent

Diagnosis must have been made no more than 24 months after completion of prior treatment with intravesical immunotherapy or chemotherapy

If carcinoma in situ is current or previous diagnosis, the biopsies must be obtained from at least 4 sites (bladder mapping)

If prostatic urothelial biopsy discloses carcinoma in situ, transurethral prostatic resection must be carried out prior to study

Papillary disease must have undergone complete transurethral resection (TURBT) within 28 days before study

--Prior/Concurrent Therapy--

Biologic therapy:

• See Disease Characteristics
• No concurrent biological response modifier therapy

Chemotherapy:

• See Disease Characteristics
• Prior oral bropirimine for bladder cancer allowed
• No prior AD 32 for bladder cancer
• No other intravenously administered systemic chemotherapy for bladder cancer
• No concurrent chemotherapy for any other malignancy

Endocrine therapy: No concurrent hormonal therapy

Radiotherapy:

• No prior radiotherapy
• No concurrent radiotherapy

Surgery: See Disease Characteristics

--Patient Characteristics--

Age: 18 and over

Performance status: ECOG 0-1

Life expectancy: Not specified

Hematopoietic:

• WBC greater than 4,000/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• Bilirubin less than 2 times upper limit of normal (ULN)
• SGOT and SGPT less than 3 times ULN

Renal: Creatinine no greater than 2.5 mg/dL

Other:

• Normal upper tract (ureter and renal pelvic) evaluation within 6 months
• No known sensitivity to anthracyclines or to Cremophor EL HIV negative
• No known AIDS or HIV-1 associated complex
• No other significant concurrent illness
• No other prior malignancy within the past 3 years except superficial bladder cancer, adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix
• Not pregnant or nursing
• Fertile patients must use effective contraception

Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
New Jersey
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07018-1095,  United States
Pennsylvania
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
Wisconsin
      CCOP - Green Bay, Green Bay,  Wisconsin,  54301,  United States
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705,  United States
      Veterans Affairs Medical Center - Milwaukee (Zablocki), Milwaukee,  Wisconsin,  53295,  United States

Study chairs or principal investigators

Jeffrey Mark Ignatoff,  Study Chair,  Eastern Cooperative Oncology Group   

Study ID Numbers:  CDR0000065892; E-3897
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003129
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08