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

Primary Purpose

Bladder Adenocarcinoma, Bladder Squamous Cell Carcinoma, Bladder Urothelial Carcinoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Recombinant Fowlpox-TRICOM Vaccine
Recombinant Fowlpox GM-CSF Vaccine Adjuvant
Therapeutic Conventional Surgery
Pharmacological Study
Laboratory Biomarker Analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Adenocarcinoma

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have a histologically documented bladder cancer including: transitional cell carcinoma, adenocarcinoma, or squamous cell carcinoma including carcinoma in situ (CIS) requiring cystectomy as a standard therapy for his/her tumor stage and be scheduled for this surgical procedure; patients should not be candidates for neoadjuvant chemotherapy Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Estimated life expectancy 6 or more months Prior therapy with intravesical Bacille Calmette-Guerin (BCG) and/or chemotherapy is allowed; patient must be at least 2 months beyond the instillation of any prior intravesical agent; patients should not have received systemic chemotherapy, radiation therapy, immunotherapy or systemic doses of steroids for at least 4 weeks prior to starting vaccination and have recovered from all acute toxicities of previous treatment; patients who have received neoadjuvant chemotherapy or radiation therapy to the bladder will be ineligible for this study Serum creatinine < 1.5 mg/dl or a creatinine clearance > 60 ml/min Bilirubin < 2.0 mg/dl Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 x normal range Absolute neutrophil count (ANC) > 1500/mm^3 Platelets > 75000/mm^3 Patients must not have known immunodeficiency disorder (acquired immunodeficiency syndrome [AIDS], severe combined immunodeficiency [SCID], Wiskott-Aldrich syndrome, etc.); study candidates will not be specifically screened for these, unless clinically indicated; if indicated, the referring physician will do the evaluation No active/uncontrolled infections Pregnant women or nursing mothers are ineligible; women with reproductive potential must have negative pregnancy test and are prohibited from sexual intercourse during this study (while receiving vaccine and at least 1 month following last dose); sexual abstinence (as opposed to contraception only) is necessary; similarly, male patients also must avoid sex for the same period as above No uncontrolled psychiatric illness or medical illness that the principal investigator feels will compromise the patient's tolerance of the study treatment Patients must be informed of the investigational nature of this study and must give written informed consent in accordance with institutional and federal guidelines; patients who cannot provide informed consent will not be eligible for the study Exclusion Criteria: Altered immune-competence: Current or imminent steroid therapy or active antibiotic therapy (antibiotics given for prophylaxis are allowed) Immune deficiency disease or immunosuppressive therapy in the patient Present or history of an autoimmune disease in the patient (e.g. autoimmune neutropenia, thrombocytopenia, or hemolytic anemia; systemic lupus erythematosus, Sjogren syndrome, or scleroderma; myasthenia gravis; Goodpasture syndrome; Addison's disease, Hashimoto's thyroiditis, active Graves' disease, or other diseases which qualify as autoimmune in origin) History of allergy to eggs as this vaccine is manufactured in chicken embryo cells Patients with any presence of liver function abnormalities, exposure to toxins, ongoing alcohol consumption, history of liver disease and/or history of hepatitis that may suggest persistent disease Any concurrent active second malignancy or any malignant tumor within the prior 5 years with the exception of a superficial squamous or basal cell skin carcinoma or in situ carcinoma of the cervix or prostate Pregnancy Patients with active ischemic heart disease (i.e. class III or IV cardiac disease-New York Heart Association), a recent history of myocardial infarction (within the last 6 months), history of congestive heart failure, ventricular arrhythmias or other arrhythmias requiring therapy

Sites / Locations

  • Rutgers Cancer Institute of New Jersey

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm A (rf-GM-CSF, closed to accrual 10/2004)

Arm B (rf-TRICOM, closed to accrual 10/2004)

Arm C (rfTRICOM and rf-GM-CSF)

Arm Description

Patients receive recombinant fowlpox GM-CSF vaccine adjuvant intravesically over 2 hours for 4 weekly doses (on days 1, 8, 15, and 22) with the last dose given 4-6 days prior to cystectomy.

Patients receive recombinant fowlpox-TRICOM vaccine intravesically over 2 hours for 4 weekly doses (on days 1, 8, 15, and 22) with the last dose given 4-6 days prior to cystectomy.

Patients receive recombinant fowlpox-TRICOM vaccine combined with recombinant fowlpox GM-CSF vaccine adjuvant intravesically over 2 hours for 4 weekly doses (on days 1, 8, 15, and 22) with the last dose given 4-6 days prior to cystectomy.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC)

Secondary Outcome Measures

Full Information

First Posted
November 4, 2003
Last Updated
December 22, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00072137
Brief Title
Neoadjuvant Intravesical Vaccine Therapy in Treating Patients With Bladder Carcinoma Who Are Undergoing Cystectomy
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2013
Overall Recruitment Status
Terminated
Study Start Date
October 2003 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase I trial studies the side effects and best dose of vaccine therapy given directly into the bladder in treating patients who are undergoing surgery to remove all or part of the bladder. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Giving a vaccine directly into the bladder before surgery may cause a stronger immune response and keep tumor cells from coming back after surgery.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the safety of intravesical administration of recombinant fowlpox virus encoding three different costimulatory molecules (B7.1, ICAM-1,LFA-3) called TRICOM (-rF-TRICOM) (recombinant fowlpox-TRICOM vaccine) and/or recombinant fowlpox encoding sargramostim (GM-CSF) (rF-GM-CSF) (recombinant fowlpox GM-CSF vaccine adjuvant) in the treatment of patients with carcinoma of the bladder scheduled for cystectomy. SECONDARY OBJECTIVES: I. Determine the kinetics of viral infection and gene function as well as host response to intravesical recombinant fowlpox virus in the treatment of bladder cancer. OUTLINE: This is a dose-escalation study. Patients are alternately assigned to Arms A and B. Once Arms A and B have finished accrual, patients are assigned to Arm C. ARM A (closed to accrual 10/2004): Patients receive recombinant fowlpox GM-CSF vaccine adjuvant intravesically over 2 hours for 4 weekly doses (on days 1, 8, 15, and 22) with the last dose given 4-6 days prior to cystectomy. ARM B (closed to accrual 10/2004): Patients receive recombinant fowlpox-TRICOM vaccine intravesically over 2 hours for 4 weekly doses (on days 1, 8, 15, and 22) with the last dose given 4-6 days prior to cystectomy. ARM C: Patients receive recombinant fowlpox-TRICOM vaccine combined with recombinant fowlpox GM-CSF vaccine adjuvant intravesically over 2 hours for 4 weekly doses (on days 1, 8, 15, and 22) with the last dose given 4-6 days prior to cystectomy. In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. All patients undergo cystectomy 4-6 days following the last intravesical instillation. After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Adenocarcinoma, Bladder Squamous Cell Carcinoma, Bladder Urothelial Carcinoma, Recurrent Bladder Carcinoma, Stage I Bladder Cancer, Stage II Bladder Cancer, Stage III Bladder Cancer, Stage IV Bladder Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (rf-GM-CSF, closed to accrual 10/2004)
Arm Type
Experimental
Arm Description
Patients receive recombinant fowlpox GM-CSF vaccine adjuvant intravesically over 2 hours for 4 weekly doses (on days 1, 8, 15, and 22) with the last dose given 4-6 days prior to cystectomy.
Arm Title
Arm B (rf-TRICOM, closed to accrual 10/2004)
Arm Type
Experimental
Arm Description
Patients receive recombinant fowlpox-TRICOM vaccine intravesically over 2 hours for 4 weekly doses (on days 1, 8, 15, and 22) with the last dose given 4-6 days prior to cystectomy.
Arm Title
Arm C (rfTRICOM and rf-GM-CSF)
Arm Type
Experimental
Arm Description
Patients receive recombinant fowlpox-TRICOM vaccine combined with recombinant fowlpox GM-CSF vaccine adjuvant intravesically over 2 hours for 4 weekly doses (on days 1, 8, 15, and 22) with the last dose given 4-6 days prior to cystectomy.
Intervention Type
Biological
Intervention Name(s)
Recombinant Fowlpox-TRICOM Vaccine
Other Intervention Name(s)
Recombinant Fowlpox-TRICOM, rF-TRICOM (B7.1.iCAM1-LFA3-Fowlpox)
Intervention Description
Given intravesically
Intervention Type
Biological
Intervention Name(s)
Recombinant Fowlpox GM-CSF Vaccine Adjuvant
Other Intervention Name(s)
Fowlpox-Sargramostim, rF-GM-CSF, rF-Sargramostim
Intervention Description
Given intravesically
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Conventional Surgery
Intervention Description
Undergo cystectomy
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC)
Time Frame
Up to 39 days

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have a histologically documented bladder cancer including: transitional cell carcinoma, adenocarcinoma, or squamous cell carcinoma including carcinoma in situ (CIS) requiring cystectomy as a standard therapy for his/her tumor stage and be scheduled for this surgical procedure; patients should not be candidates for neoadjuvant chemotherapy Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Estimated life expectancy 6 or more months Prior therapy with intravesical Bacille Calmette-Guerin (BCG) and/or chemotherapy is allowed; patient must be at least 2 months beyond the instillation of any prior intravesical agent; patients should not have received systemic chemotherapy, radiation therapy, immunotherapy or systemic doses of steroids for at least 4 weeks prior to starting vaccination and have recovered from all acute toxicities of previous treatment; patients who have received neoadjuvant chemotherapy or radiation therapy to the bladder will be ineligible for this study Serum creatinine < 1.5 mg/dl or a creatinine clearance > 60 ml/min Bilirubin < 2.0 mg/dl Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 x normal range Absolute neutrophil count (ANC) > 1500/mm^3 Platelets > 75000/mm^3 Patients must not have known immunodeficiency disorder (acquired immunodeficiency syndrome [AIDS], severe combined immunodeficiency [SCID], Wiskott-Aldrich syndrome, etc.); study candidates will not be specifically screened for these, unless clinically indicated; if indicated, the referring physician will do the evaluation No active/uncontrolled infections Pregnant women or nursing mothers are ineligible; women with reproductive potential must have negative pregnancy test and are prohibited from sexual intercourse during this study (while receiving vaccine and at least 1 month following last dose); sexual abstinence (as opposed to contraception only) is necessary; similarly, male patients also must avoid sex for the same period as above No uncontrolled psychiatric illness or medical illness that the principal investigator feels will compromise the patient's tolerance of the study treatment Patients must be informed of the investigational nature of this study and must give written informed consent in accordance with institutional and federal guidelines; patients who cannot provide informed consent will not be eligible for the study Exclusion Criteria: Altered immune-competence: Current or imminent steroid therapy or active antibiotic therapy (antibiotics given for prophylaxis are allowed) Immune deficiency disease or immunosuppressive therapy in the patient Present or history of an autoimmune disease in the patient (e.g. autoimmune neutropenia, thrombocytopenia, or hemolytic anemia; systemic lupus erythematosus, Sjogren syndrome, or scleroderma; myasthenia gravis; Goodpasture syndrome; Addison's disease, Hashimoto's thyroiditis, active Graves' disease, or other diseases which qualify as autoimmune in origin) History of allergy to eggs as this vaccine is manufactured in chicken embryo cells Patients with any presence of liver function abnormalities, exposure to toxins, ongoing alcohol consumption, history of liver disease and/or history of hepatitis that may suggest persistent disease Any concurrent active second malignancy or any malignant tumor within the prior 5 years with the exception of a superficial squamous or basal cell skin carcinoma or in situ carcinoma of the cervix or prostate Pregnancy Patients with active ischemic heart disease (i.e. class III or IV cardiac disease-New York Heart Association), a recent history of myocardial infarction (within the last 6 months), history of congestive heart failure, ventricular arrhythmias or other arrhythmias requiring therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Weiss
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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