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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00072137
First received: November 4, 2003
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

This phase I trial is studying the side effects and best dose of intravesical vaccine therapy in treating patients who are undergoing cystectomy for bladder cancer. 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.


Condition Intervention Phase
Adenocarcinoma of the Bladder
Recurrent Bladder Cancer
Squamous Cell Carcinoma of the Bladder
Stage 0 Bladder Cancer
Stage I Bladder Cancer
Stage II Bladder Cancer
Stage III Bladder Cancer
Transitional Cell Carcinoma of the Bladder
Procedure: conventional surgery
Biological: recombinant fowlpox-TRICOM vaccine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Intravesical Recombinant Fowlpox - GM-CSF (rF-GM-CSF) and/or Recombinant Fowlpox-TRICOM (rF-TRICOM) in Patients With Bladder Carcinoma Scheduled for Cystectomy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC) [ Time Frame: Up to 39 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 42
Study Start Date: October 2003
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (surgery, vaccine)

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.

Procedure: conventional surgery
Undergo surgery
Other Name: surgery, conventional
Biological: recombinant fowlpox-TRICOM vaccine
Given IV
Other Name: rF-TRICOM (B7.1.iCAM1-LFA3-Fowlpox)

Detailed Description:

PRIMARY OBJECTIVES:

I. 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.

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

SECONDARY OBJECTIVES:

I. 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 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • ECOG 0-1
  • Life expectancy >= 6 months
  • 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
  • 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 other immunodeficiency disease
  • 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
  • At least 4 weeks since prior immunotherapy
  • At least 2 months since prior intravesical BCG
  • No prior neoadjuvant chemotherapy
  • At least 4 weeks since prior systemic chemotherapy
  • At least 2 months since prior intravesical chemotherapy
  • No concurrent or imminent steroid therapy
  • No prior radiotherapy to the bladder
  • At least 4 weeks since prior radiotherapy
  • Recovered from prior therapy
  • No concurrent acetaminophen
  • No concurrent active antibiotic therapy except as prophylaxis
  • No concurrent immunosuppressive therapy
  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count greater than 75,000/mm^3
  • 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
  • Creatinine less than 1.5 mg/dL OR creatinine clearance greater than 60 mL/min
  • At least 4 weeks since prior systemic steroids
  • No immunodeficiency disorder (e.g., AIDS, SCID, or Wiskott-Aldrich syndrome)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00072137

Locations
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
Investigators
Principal Investigator: Robert Weiss Rutgers Cancer Institute of New Jersey
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00072137     History of Changes
Other Study ID Numbers: NCI-2009-00020, 050301, CDR0000335473, U01CA132194
Study First Received: November 4, 2003
Last Updated: July 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Squamous Cell
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Squamous Cell
Metronidazole
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antiprotozoal Agents
Antiparasitic Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 18, 2014