search
Back to results

Vaccine Therapy in Treating Patients With Stage III-IV or Recurrent Ovarian Cancer

Primary Purpose

Stage III Ovarian Epithelial Cancer, Stage III Ovarian Germ Cell Tumor, Stage IV Ovarian Epithelial Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine
laboratory biomarker analysis
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage III Ovarian Epithelial Cancer focused on measuring Ovarian Cancer, Vaccine, Stage III, Stage IV, Remission

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with advanced stage (III/IV) or recurrent ovarian cancer who have been treated to complete remission with standard therapies including primary debulking surgery
  • Cancer antigen 125 (CA-125) level within normal limits for the testing laboratory must be documented 90 days prior to enrollment when the assessment of CA-125 is applicable
  • Patients must be at least 28 days post cytotoxic chemotherapy, and/or monoclonal antibody therapy, prior to enrollment
  • Patients must be at least 28 days post systemic steroids prior to enrollment
  • Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status Score of =< 2
  • Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment
  • Estimated life expectancy of more than 6 months
  • White Blood Cell (WBC) >= 3000/mm^3
  • Hemoglobin (Hgb) >= 10 mg/dl
  • Hematocrit (Hct) >= 28%
  • Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min
  • Total bilirubin =< 2.5 mg/dl
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3 times upper limit of normal (ULN)
  • Blood glucose < 1.5 ULN

Exclusion Criteria:

  • Patients with any of the following cardiac conditions: symptomatic restrictive cardiomyopathy; unstable angina within 4 months prior to enrollment; New York Heart Association functional class III-IV heart failure on active treatment; symptomatic pericardial effusion
  • Uncontrolled diabetes
  • Patients with any contraindication to receiving sargramostim (rhuGM-CSF) based products
  • Ovarian cancer of a low malignant potential phenotype or clear cell histology
  • Patients with any clinically significant autoimmune disease uncontrolled with treatment
  • Patients who are currently receiving an anti-IGF-IR monoclonal antibody as part of their treatment regimen
  • Patients who are simultaneously enrolled in any other treatment study
  • All subjects able to bear children

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine)

Arm Description

Patients receive pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine ID monthly for 3 months.

Outcomes

Primary Outcome Measures

Safety as assessed per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Demographic and background characteristics obtained at enrollment will be listed and summarized. The type and grade of toxicities noted during the immunization regimen will be summarized. All adverse events noted by the investigator will be tabulated according to the affected body system. Descriptive statistics will be used to summarize changes from baseline in clinical laboratory parameters.

Secondary Outcome Measures

Immunogenicity, via cellular immune response and humoral immune response, as assessed by the generation of IGFBP-2 specific T cells and IgG antibodies
Cellular immune response will be defined by the magnitude of the Th1 antigen specific immune response using IFN-gamma enzyme-linked immunosorbent spot (ELISPOT). Humoral immune response will be measured by enzyme-linked immunosorbent assay (ELISA) and serum antibody avidity for IGFBP-2 using ELISA to determine an avidity index (AI) before and after vaccination. Spearman's correlation coefficient will be used to estimate the correlation between two continuous measures.
Epitope spreading with the generation of an IGFBP-2 Th1 immune response
Peripheral blood mononuclear cells (PBMC) will be assessed by ELISPOT for immunity to a panel of immunogenic ovarian cancer related proteins: topoisomerase II-alpha (a), p53, IGF-IR, FASCIN-1, and MMP-7. Epitope spreading will have been considered to occur if new immune responses are generated to any of these antigens during the course of the study. In addition, epitope spreading and T regulatory cells will be defined as present or absent, and the probability of each will be estimated as a simple proportion as above with toxicity.
Levels of regulatory T- cells (Tregs) over the course of immunization to detect modulation of Tregs with vaccination
Assessed by flow cytometry of PBMC. In addition, epitope spreading and T regulatory cells will be defined as present or absent, and the probability of each will be estimated as a simple proportion as above with toxicity.
Disease-free survival
A questionnaire will be sent to the patient's primary oncologist requesting laboratory evaluation of toxicity, CA-125, and the patient's disease free and overall survival status.
Overall survival
A questionnaire will be sent to the patient's primary oncologist requesting laboratory evaluation of toxicity, CA-125, and the patient's disease free and overall survival status

Full Information

First Posted
March 7, 2011
Last Updated
February 22, 2021
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT01322802
Brief Title
Vaccine Therapy in Treating Patients With Stage III-IV or Recurrent Ovarian Cancer
Official Title
A Phase I Trial of the Safety and Immunogenicity of a DNA Plasmid Based Vaccine Encoding the Amino Acids 1-163 of Insulin-Like Growth Factor Binding Protein-2 (IGFBP-2) in Patients With Advanced Ovarian Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
March 6, 2012 (Actual)
Primary Completion Date
January 9, 2015 (Actual)
Study Completion Date
December 1, 2020 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase I trial is studying the side effects of vaccine therapy in treating patients with stage III-IV or recurrent ovarian cancer. Vaccines made from deoxyribonucleic acid (DNA) may help the body build an effective immune response to kill tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the safety of an insulin like growth factor binding protein 2 (IGFBP-2) Th polyepitope plasmid based vaccine in patients with advanced stage or recurrent ovarian cancer. SECONDARY OBJECTIVES: I. To determine the immunogenicity of IGFBP-2 Th polyepitope plasmid based vaccine in patients with advanced stage or recurrent ovarian cancer. II. To determine whether intermolecular epitope spreading occurs with the generation of an IGFBP-2 specific Th1 immune response. III. To determine whether IGFBP-2 vaccination modulates T regulatory cells. OUTLINE: Patients receive pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine intradermally (ID) monthly for 3 months. After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months, and then every 6 months for 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III Ovarian Epithelial Cancer, Stage III Ovarian Germ Cell Tumor, Stage IV Ovarian Epithelial Cancer, Stage IV Ovarian Germ Cell Tumor
Keywords
Ovarian Cancer, Vaccine, Stage III, Stage IV, Remission

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine)
Arm Type
Experimental
Arm Description
Patients receive pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine ID monthly for 3 months.
Intervention Type
Biological
Intervention Name(s)
pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine
Intervention Description
Given ID
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Safety as assessed per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Description
Demographic and background characteristics obtained at enrollment will be listed and summarized. The type and grade of toxicities noted during the immunization regimen will be summarized. All adverse events noted by the investigator will be tabulated according to the affected body system. Descriptive statistics will be used to summarize changes from baseline in clinical laboratory parameters.
Time Frame
Up to 16 months
Secondary Outcome Measure Information:
Title
Immunogenicity, via cellular immune response and humoral immune response, as assessed by the generation of IGFBP-2 specific T cells and IgG antibodies
Description
Cellular immune response will be defined by the magnitude of the Th1 antigen specific immune response using IFN-gamma enzyme-linked immunosorbent spot (ELISPOT). Humoral immune response will be measured by enzyme-linked immunosorbent assay (ELISA) and serum antibody avidity for IGFBP-2 using ELISA to determine an avidity index (AI) before and after vaccination. Spearman's correlation coefficient will be used to estimate the correlation between two continuous measures.
Time Frame
Up to 16 months
Title
Epitope spreading with the generation of an IGFBP-2 Th1 immune response
Description
Peripheral blood mononuclear cells (PBMC) will be assessed by ELISPOT for immunity to a panel of immunogenic ovarian cancer related proteins: topoisomerase II-alpha (a), p53, IGF-IR, FASCIN-1, and MMP-7. Epitope spreading will have been considered to occur if new immune responses are generated to any of these antigens during the course of the study. In addition, epitope spreading and T regulatory cells will be defined as present or absent, and the probability of each will be estimated as a simple proportion as above with toxicity.
Time Frame
Up to 16 months
Title
Levels of regulatory T- cells (Tregs) over the course of immunization to detect modulation of Tregs with vaccination
Description
Assessed by flow cytometry of PBMC. In addition, epitope spreading and T regulatory cells will be defined as present or absent, and the probability of each will be estimated as a simple proportion as above with toxicity.
Time Frame
Up to 16 months
Title
Disease-free survival
Description
A questionnaire will be sent to the patient's primary oncologist requesting laboratory evaluation of toxicity, CA-125, and the patient's disease free and overall survival status.
Time Frame
Up to 5 years
Title
Overall survival
Description
A questionnaire will be sent to the patient's primary oncologist requesting laboratory evaluation of toxicity, CA-125, and the patient's disease free and overall survival status
Time Frame
Up to 5 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with advanced stage (III/IV) or recurrent ovarian cancer who have been treated to complete remission with standard therapies including primary debulking surgery Cancer antigen 125 (CA-125) level within normal limits for the testing laboratory must be documented 90 days prior to enrollment when the assessment of CA-125 is applicable Patients must be at least 28 days post cytotoxic chemotherapy, and/or monoclonal antibody therapy, prior to enrollment Patients must be at least 28 days post systemic steroids prior to enrollment Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status Score of =< 2 Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment Estimated life expectancy of more than 6 months White Blood Cell (WBC) >= 3000/mm^3 Hemoglobin (Hgb) >= 10 mg/dl Hematocrit (Hct) >= 28% Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min Total bilirubin =< 2.5 mg/dl Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3 times upper limit of normal (ULN) Blood glucose < 1.5 ULN Exclusion Criteria: Patients with any of the following cardiac conditions: symptomatic restrictive cardiomyopathy; unstable angina within 4 months prior to enrollment; New York Heart Association functional class III-IV heart failure on active treatment; symptomatic pericardial effusion Uncontrolled diabetes Patients with any contraindication to receiving sargramostim (rhuGM-CSF) based products Ovarian cancer of a low malignant potential phenotype or clear cell histology Patients with any clinically significant autoimmune disease uncontrolled with treatment Patients who are currently receiving an anti-IGF-IR monoclonal antibody as part of their treatment regimen Patients who are simultaneously enrolled in any other treatment study All subjects able to bear children
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary Disis
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Vaccine Therapy in Treating Patients With Stage III-IV or Recurrent Ovarian Cancer

We'll reach out to this number within 24 hrs