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.

Study Overview

• Status: Completed
• Conditions: Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor
• Intervention / Treatment: Other: laboratory biomarker analysis; Biological: pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine

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.

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Other: laboratory biomarker analysis; Correlative studies; Biological: pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine; Given ID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	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.	Up to 16 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity, via cellular immune response and humoral immune response, as assessed by the generation of IGFBP-2 specific T cells and IgG antibodies	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.	Up to 16 months
Epitope spreading with the generation of an IGFBP-2 Th1 immune response	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.	Up to 16 months
Levels of regulatory T- cells (Tregs) over the course of immunization to detect modulation of Tregs with vaccination	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.	Up to 16 months
Disease-free survival	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.	Up to 5 years
Overall survival	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	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2012
• Primary Completion (Actual): January 9, 2015
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: March 7, 2011
• First Submitted That Met QC Criteria: March 23, 2011
• First Posted (Estimate): March 25, 2011

Study Record Updates

• Last Update Posted (Actual): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 22, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Vaccine; Remission; Ovarian Cancer; Stage III; Stage IV
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Germinoma
• Other Study ID Numbers: 7396 (Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); 134; NCI-2011-00099 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RG7212000 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)