Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Neoadjuvant Intravesical Vaccine Therapy in Treating Patients With Bladder Carcinoma Who Are Undergoing Cystectomy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Active	Not specified	NCI	CINJ-3909 NCI-5585, NCT00072137, 5585

Objectives

Primary

1. 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.
2. Determine the dose-limiting toxic effects of these regimens in these patients.

Secondary

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

Entry 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

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 acetaminophen
• No concurrent active antibiotic therapy except as prophylaxis
• No concurrent immunosuppressive therapy

Patient Characteristics:

Age

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm³
• Platelet count greater than 75,000/mm³

Hepatic

• No history of liver disease and/or history of hepatitis that may suggest persistent disease
• SGOT less than 2 times normal
• Bilirubin less than 2.0 mg/dL
• No presence of liver function abnormalities

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 prior exposure to liver toxins
• No ongoing alcohol consumption or exposure to other liver toxins
• 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

Expected Enrollment

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

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 4-5 days 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.

Trial Contact Information

Trial Lead Organizations

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

Edmund Lattime, PhD, Protocol chair		Ph: 732-235-8588

U.S.A.
New Jersey
	New Brunswick
	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
		Clinical Trials Office - Cancer Institute of New Jersey	Ph:  732-235-8675

Registry Information
Official Title		Phase I Study of Intravesical Recombinant Fowlpox - GM-CSF (rF-GM-CSF) and/or Recombinant Fowlpox-Tricom (rF-TRICOM) in Patients with Muscle-Invasive Bladder Carcinoma
Trial Start Date		2003-10-21
Trial Completion Date		2005-07-12 (estimated)
Registered in ClinicalTrials.gov		NCT00072137
Date Submitted to PDQ		2003-09-18
Information Last Verified		2009-01-30
NCI Grant/Contract Number		CA74543, CA72720