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

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

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.

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.

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