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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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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

Intervention / Treatment
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* Biological: pNGVL3-hICD vaccine
* Biological: sargramostim
* Other: flow cytometry
* Other: immunologic technique
* Other: immunoenzyme technique
* Genetic: protein expression analysis
* Procedure: biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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<br>* Plasmid-based DNA vaccine, given intradermally<br>Biological: sargramostim<br>* Given intradermally<br>* Other names: rhu GM-CFS;Other: flow cytometry<br>* Correlative studies<br>Other: immunologic technique<br>* Correlative studies<br>* Other names: laboratory methods, immunological;Other: immunoenzyme technique<br>* Undergo ELIspot (correlative studies)<br>* Other names: immunoenzyme techniques;Genetic: protein expression analysis<br>* Undergo ELISA (correlative studies)<br>Procedure: biopsy<br>* Undergo punch biopsy (correlative studies)<br>* Other names: biopsies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as measured by NCI CTCAE v 3.0 |  | From baseline | 
| Immune response |  | From baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of dose on immunologic response |  | From baseline to month 15 | 
| Persistence of DNA at the injection site |  | At 1 and 6 months after last vaccination |