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
N/A
N/A
Both
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
Trial Information
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
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.
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)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC)
Outcome Time Frame:
Up to 39 days
Safety Issue:
Yes
Principal Investigator
Robert Weiss
Investigator Role:
Principal Investigator
Investigator Affiliation:
Cancer Institute of New Jersey
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00020
NCT ID:
NCT00072137
Start Date:
October 2003
Completion Date:
Related Keywords:
- 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
- Adenocarcinoma
- Adenocarcinoma, Mucinous
- Urinary Bladder Neoplasms
- Carcinoma
- Carcinoma, Squamous Cell
- Carcinoma, Transitional Cell
Name | Location |
|---|---|
| Cancer Institute of New Jersey | New Brunswick, New Jersey 08901 |
