Clinical Trial: Vaccine Therapy in Treating Patients With Stage III-IV or Recurrent Ovarian Cancer
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
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 Ovari
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 Summary:
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.
Sponsor: University of Washington
Current Primary Outcome: 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 ]
Original Primary Outcome:
- Safety as assessed using National Cancer Institute (NCI) common toxicity criteria [ Time Frame: At second and third vaccine administrations and month 4 ]
- 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: At baseline and months 4, 9, and 15 ]
Current Secondary Outcome:
- 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
Original Secondary Outcome:
- Epitope spreading with the generation of an IGFBP-2 Th1 immune response [ Time Frame: At baseline and months 4, 9, and 15 ]
- Levels of regulatory T- cells (Tregs) over the course of immunization to detect modulation of Tregs with vaccination [ Time Frame: At baseline and months 4, 9, and 15Up ]
Information By: University of Washington
Dates:
Date Received: March 7, 2011
Date Started: March 6, 2012
Date Completion:
Last Updated: April 3, 2017
Last Verified: April 2017