Scientific 134

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 Contact
Stephanie Parker | 866.932.8588 | E-Mail
Rationale
IGFBP-2 can be detected in the sera of OC patients and is emerging as a potentially important regulator of OC invasiveness and the development of metastasis. Eradication of tumor cells expressing IGFBP-2, by the immune system, could be beneficial in preventing disease relapse or tumor spread. Vaccine strategies designed to stimulate T cells could result in the ability for the immune system to kill tumor cells. The inflammation created by the T cells can turn on the immune system to start responding to protein expressed by the patientís tumor other than IGFBP-2. This ìepitope spreadingî could result in greater tumor cell killing.
Study Population / Indication
  1. Patients with stage III or IV ovarian cancer who have been treated to complete remission with standard therapies including primary debulking surgery
  2. Patients must be at least 28 days post cytotoxic chemotherapy, systemic steroids, and/or monoclonal antibody therapy, prior to enrollment
  3. Patients must have recovered from major infections and/or surgical procedures
  4. Normal CA-125 level and adequate laboratory values when applicable
  5. Patients cannot have uncontrolled diabetes or any other clinically significant autoimmune disease
  6. Patients cannot be receiving an anti-IGF-IR monoclonal antibody in their current treatment
  7. Patients cannot be simultaneously enrolled in any other treatment study
  8. Patients with a low malignant potential phenotype or clear cell histology are excluded
Number of Patients: This study will accrue a total of 22 patients.
Start Date: March 2012
Study Location: University of Washington Medical Center | 1959 NE Pacific Street | Seattle, WA 98195
Objectives
  1. To determine the safety and immunogenenicity of an IGFBP-2 polyepitope plasmid based vaccine in patients with advanced stage ovarian cancer
  2. To determine whether epitope spreading occurs with the generation of an IGFBP-2 specific immunity
  3. To determine whether IGFBP-2 vaccination decreases the immune suppression seen in ovarian cancer
Outcome Measures
Primary endpoint is toxicity.

The type and grade of toxicities noted during the immunization regimen will be summarized. We have chosen the sample size of 22 subjects so that if no toxicities occur, the probability of such an occurrence is at least 90% if the true toxicity rate. The study will continue and be deemed sufficiently safe as long as the observed toxicity rate is consistent with a true grade 3 rate of 15% or less and a true grade 4 rate of 5% or less.

Secondary endpoint is immunologic response rate.

The sample size of 22 will allow 80% confidence that the estimated response rate is within at least .14 of the true response rate. If 11 of the 22 patients have a response, then 11 responders and 11 non-responders will yield 91% power to observe a statistically significant difference in continuous measures between responders and non-responders if the true effect size in 1.5. 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.

Clinical Description
ClinicalTrials.gov Identifier: NCT01322802

Clinical Trials Contact

For more information regarding our trials, please call our Patient Coordinator

Stephanie Parker
866-932-8588
Email