RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Placing a vaccine directly into the bladder may cause a stronger immune response and kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of neoadjuvant intravesical vaccine therapy in treating patients who are undergoing cystectomy for bladder carcinoma (cancer).

Condition	Treatment or Intervention	Phase
Bladder Cancer	Drug: fowlpox-TRICOM vaccine  Drug: recombinant fowlpox GM-CSF vaccine  Procedure: biological response modifier therapy  Procedure: conventional surgery  Procedure: neoadjuvant therapy  Procedure: recombinant viral vaccine  Procedure: surgery  Procedure: vaccine therapy	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the maximum tolerated dose of neoadjuvant intravesical recombinant fowlpox-TRICOM vaccine and/or recombinant fowlpox-sargramostim vaccine in patients with bladder carcinoma who are scheduled for cystectomy.
• Determine the dose-limiting toxic effects of these regimens in these patients.

Secondary

• Determine the local and systemic immunologic response in patients treated with these regimens.

OUTLINE: This is an open-label, dose-escalation study. Patients are alternately assigned to regimens A and B. Once regimens A and B have finished accrual, patients are assigned to regimen C.

• Regimen A: Patients receive recombinant fowlpox-sargramostim vaccine intravesically on days 1, 8, 15, and 22 for a total of 4 doses.
• Regimen B: Patients receive recombinant fowlpox-TRICOM vaccine intravesically on days 1, 8, 15, and 22 for a total of 4 doses.
• Regimen C: Patients receive recombinant fowlpox-TRICOM vaccine combined with recombinant fowlpox-sargramostim vaccine intravesically on days 1, 8, 15, and 22 for a total of 4 doses. In all regimens, the vaccine(s) is delivered into the bladder by urinary catheter and retained for 2 hours. Treatment continues in the absence of disease progression or unacceptable toxicity.

In all regimens, patients undergo cystectomy within 48-96 hours after the last (4th) intravesical instillation.

Cohorts of 3-6 patients in each regimen receive escalating doses of recombinant fowlpox-sargramostim vaccine and/or recombinant fowlpox-TRICOM vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 6 months for 2 years and then annually for 3 years.

PROJECTED ACCRUAL: Approximately 24-42 patients will be accrued for this study within 12-18 months.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed cancer of the urinary bladder, including the following cellular types:
• Transitional cell carcinoma
• Adenocarcinoma
• Squamous cell carcinoma
• Requires cystectomy as standard therapy and scheduled to undergo surgery
• Ineligible for neoadjuvant chemotherapy

PATIENT CHARACTERISTICS: Age

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 75,000/mm^3

Hepatic

• SGOT less than 2 times normal
• Bilirubin less than 2.0 mg/dL

Renal

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular

• No active ischemic heart disease (i.e., New York Heart Association class III or IV cardiac disease)
• No myocardial infarction within the past 6 months
• No history of congestive heart failure
• No history of ventricular arrhythmias or other arrhythmias requiring therapy

Immunologic

• No history of autoimmune disease, including, but not limited to, the following:
• Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia
• Systemic lupus erythematosus
• Sjögren's syndrome
• Scleroderma
• Myasthenia gravis
• Goodpasture's syndrome
• Addison's disease
• Hashimoto's thyroiditis
• Active Graves' disease
• No immunodeficiency disorder (e.g., AIDS, SCID, or Wiskott-Aldrich syndrome)
• No other immunodeficiency disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• All patients must abstain from sexual intercourse during and for at least 1 month after final treatment dose
• No known allergy to eggs
• No active uncontrolled infection
• No other active malignancy within the past 5 years except superficial squamous cell or basal cell skin cancer or carcinoma in situ of the cervix or prostate
• No other medical illness that would preclude study participation
• No uncontrolled psychiatric illness that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• At least 4 weeks since prior immunotherapy
• At least 2 months since prior intravesical BCG

Chemotherapy

• No prior neoadjuvant chemotherapy
• At least 4 weeks since prior systemic chemotherapy
• At least 2 months since prior intravesical chemotherapy

Endocrine therapy

• At least 4 weeks since prior systemic steroids
• No concurrent or imminent steroid therapy

Radiotherapy

• No prior radiotherapy to the bladder
• At least 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• No concurrent active antibiotic therapy except as prophylaxis
• No concurrent immunosuppressive therapy

New Jersey
      Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick,  New Jersey,  08903,  United States; Recruiting

Study chairs or principal investigators

Edmund Lattime, PhD,  Study Chair,  Cancer Institute of New Jersey   

Study ID Numbers:  CDR0000335473; CINJ-3909; NCI-5585; NCT00072137
Record last reviewed:  July 2004
Last Updated:  January 6, 2005
Record first received:  November 4, 2003
ClinicalTrials.gov Identifier:  NCT00072137
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08