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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- University of Washington
- Enrollment
- 25
- Locations
- 2
- Primary Endpoint
- Safety as assessed per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
Safety as assessed per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame: Up to 16 months
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 Outcomes
- Disease-free survival(Up to 5 years)
- Levels of regulatory T- cells (Tregs) over the course of immunization to detect modulation of Tregs with vaccination(Up to 16 months)
- Immunogenicity, via cellular immune response and humoral immune response, as assessed by the generation of IGFBP-2 specific T cells and IgG antibodies(Up to 16 months)
- Epitope spreading with the generation of an IGFBP-2 Th1 immune response(Up to 16 months)
- Overall survival(Up to 5 years)