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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01322802
First received: March 7, 2011
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
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 Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 22
Study Start Date: March 2012
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 ID
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01322802

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Mary Disis Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT01322802     History of Changes
Other Study ID Numbers: 7396, NCI-2011-00099, 134, 7396, P30CA015704
Study First Received: March 7, 2011
Last Updated: June 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Washington:
Ovarian Cancer
Vaccine
Stage III
Stage IV
Remission

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Germ Cell and Embryonal
Germinoma
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 31, 2014