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Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00436254
Recruitment Status : Active, not recruiting
First Posted : February 19, 2007
Last Update Posted : May 30, 2019
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

Brief Summary:
RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving vaccine therapy together with sargramostim may be an effective treatment for breast cancer and ovarian cancer. PURPOSE: This phase I trial is studying the side effects and identifying the best dose of vaccine therapy when given together with sargramostim in treating patients with stage III-IV breast cancer or ovarian cancer.

Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer Stage III Ovarian Epithelial Cancer Stage III Ovarian Germ Cell Tumor Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer Stage IV Ovarian Epithelial Cancer Stage IV Ovarian Germ Cell Tumor Biological: pNGVL3-hICD vaccine Biological: sargramostim Other: flow cytometry Other: immunologic technique Other: immunoenzyme technique Genetic: protein expression analysis Procedure: biopsy Phase 1

Detailed Description:
PRIMARY OBJECTIVES: I. To determine the safety of intradermal administration of 3 doses of a plasmid-based DNA vaccine encoding the ICD of HER2 administered with a fixed dose of GM-CSF. II. To determine whether a plasmid DNA vaccine encoding the ICD of HER2 can elicit HER2 specific immune responses. SECONDARY OBJECTIVES: I. To determine if the dose of the plasmid-based DNA vaccine effects immunologic responses. II. To determine the persistence of DNA at the site of vaccination. OUTLINE: This is a dose-escalation study of a plasmid-based DNA (pNGVL3-hICD) vaccine. Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 15 years with primary physicians.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of a DNA Plasmid Based Vaccine Encoding the HER-2/Neu Intracellular Domain in Subjects With HER-2/Neu (HER2) Overexpressing Tumors
Study Start Date : October 2001
Actual Primary Completion Date : March 2010

Arm Intervention/treatment
Experimental: Arm I
Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity.
Biological: pNGVL3-hICD vaccine
Plasmid-based DNA vaccine, given intradermally

Biological: sargramostim
Given intradermally
Other Names:
  • GM-CSF
  • granulocyte macrophage colony-stimulating factor
  • Leukine
  • Prokine
  • rhu GM-CFS

Other: flow cytometry
Correlative studies

Other: immunologic technique
Correlative studies
Other Names:
  • immunological laboratory methods
  • laboratory methods, immunological

Other: immunoenzyme technique
Undergo ELIspot (correlative studies)
Other Name: immunoenzyme techniques

Genetic: protein expression analysis
Undergo ELISA (correlative studies)

Procedure: biopsy
Undergo punch biopsy (correlative studies)
Other Name: biopsies

Primary Outcome Measures :
  1. Safety as measured by NCI CTCAE v 3.0 [ Time Frame: From baseline ]
  2. Immune response [ Time Frame: From baseline ]

Secondary Outcome Measures :
  1. Impact of dose on immunologic response [ Time Frame: From baseline to month 15 ]
  2. Persistence of DNA at the injection site [ Time Frame: At 1 and 6 months after last vaccination ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Breast cancer: stage III or stage IV breast cancer with metastasis in remission and defined as NED (no evidence of disease); stable or healing bone disease by radiologic evaluation which may include, but is not limited to, bone scan, MRI, or PET scan documented within 90 days of enrollment to study and NED status for extraskeletal metastasis
  • Ovarian cancer: stage III or stage IV ovarian cancer in first complete remission with a normal AND stable CA-125; thus, two sequential normal CA-125 values will need to be documented; a minimum of 30 days between 2 sequential CA-125 values; the most recent will be within 2 weeks of enrollment into study
  • HER2 overexpression by immunohistochemistry (IHC) of 2+ or 3+ in their primary tumor or metastasis, and if overexpression is 2+ by IHC or in the absence of IHC, then patients must have documentation of HER2 gene amplification by FISH
  • Eligible subjects must have completed appropriate treatment for their primary disease and be off cytotoxic chemotherapy and corticosteroids for at least 1 month prior to enrollment; patients with stage III/IV breast cancer who have completed chemotherapy and are continued on trastuzumab monotherapy are eligible; hormonal and bisphosphanate therapies are allowed
  • Subjects must have a Performance Status Score (Zubrod/ECOG Scale) = 0
  • All subjects must no longer be able to bear children
  • Hematocrit >= 30
  • Platelet count >= 100,000
  • WBC >= 3,000/ul
  • Creatinine =< 2.0 or creatinine clearance >= 60 ml/minute
  • Serum bilirubin < 1.5 mg/dl
  • SGOT < 2 x ULN
  • Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment or survival
  • Normal ANA, anti-dsDNA and C3
  • Patients on trastuzumab monotherapy must have adequate cardiac function as demonstrated by normal ejection fraction (EF) of MUGA scan or echocardiogram

Exclusion Criteria:

  • Subjects cannot be simultaneously enrolled on other treatment studies
  • Any contraindication to receiving GM-CSF based vaccine products
  • Prior known history of cardiac disease, specifically restrictive cardiomyopathy, unstable angina within the last 6 months prior to enrollment, New York Heart Association functional class III-IV heart or symptomatic pericardial effusion
  • Prior known history of pulmonary disease other than controlled asthma
  • Active autoimmune disease
  • Subjects cannot have active immunodeficiency disorder, e.g., HIV

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00436254

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United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
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Principal Investigator: Mary L. Disis Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

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Responsible Party: University of Washington Identifier: NCT00436254     History of Changes
Obsolete Identifiers: NCT00194662
Other Study ID Numbers: 6532
First Posted: February 19, 2007    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms, Germ Cell and Embryonal
Carcinoma, Ovarian Epithelial
Ovarian Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Immunologic Factors
Physiological Effects of Drugs