Vaccine Therapy in Treating Patients With Stage III-IV or Recurrent Ovarian Cancer
|Stage III Ovarian Epithelial Cancer Stage III Ovarian Germ Cell Tumor Stage IV Ovarian Epithelial Cancer Stage IV Ovarian Germ Cell Tumor||Biological: pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine Other: laboratory biomarker analysis||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|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|
- 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.
- Immunogenicity, via cellular immune response and humoral immune response, as assessed by the generation of IGFBP-2 specific T cells and IgG antibodies [ Time Frame: Up to 16 months ]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 [ Time Frame: Up to 16 months ]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 [ Time Frame: Up to 16 months ]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 [ Time Frame: Up to 5 years ]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 [ Time Frame: Up to 5 years ]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
|Actual Study Start Date:||March 6, 2012|
|Primary Completion Date:||January 9, 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine)
Patients receive pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine ID monthly for 3 months.
Biological: pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine
Given IDOther: laboratory biomarker analysis
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01322802
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Mary Disis||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|