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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

Phase 1
18 Years
Open (Enrolling)
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

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Trial Information

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

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.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety as measured by NCI CTCAE v 3.0

Outcome Time Frame:

From baseline

Safety Issue:


Principal Investigator

Mary L. Disis

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

October 2001

Completion Date:

Related Keywords:

  • 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
  • Breast Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Germinoma
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial



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