Back to resultsVaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer
Primary Purpose
HER2-positive Breast Cancer, Stage III Ovarian Epithelial Cancer, Stage III Ovarian Germ Cell Tumor
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
pNGVL3-hICD vaccine
sargramostim
flow cytometry
immunologic technique
immunoenzyme technique
protein expression analysis
biopsy
Sponsored by
About this trial
This is an interventional treatment trial for HER2-positive Breast Cancer
Eligibility Criteria
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
Sites / Locations
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm I
Arm Description
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.
Outcomes
Primary Outcome Measures
Safety as measured by NCI CTCAE v 3.0
Immune response
Secondary Outcome Measures
Impact of dose on immunologic response
Persistence of DNA at the injection site
Full Information
NCT ID
NCT00436254
First Posted
February 15, 2007
Last Updated
October 20, 2023
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00436254
Brief Title
Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 2001 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
December 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
pNGVL3-hICD vaccine
Intervention Description
Plasmid-based DNA vaccine, given intradermally
Intervention Type
Biological
Intervention Name(s)
sargramostim
Other Intervention Name(s)
GM-CSF, granulocyte macrophage colony-stimulating factor, Leukine, Prokine, rhu GM-CFS
Intervention Description
Given intradermally
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
immunologic technique
Other Intervention Name(s)
immunological laboratory methods, laboratory methods, immunological
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
immunoenzyme technique
Other Intervention Name(s)
immunoenzyme techniques
Intervention Description
Undergo ELIspot (correlative studies)
Intervention Type
Genetic
Intervention Name(s)
protein expression analysis
Intervention Description
Undergo ELISA (correlative studies)
Intervention Type
Procedure
Intervention Name(s)
biopsy
Other Intervention Name(s)
biopsies
Intervention Description
Undergo punch biopsy (correlative studies)
Primary Outcome Measure Information:
Title
Safety as measured by NCI CTCAE v 3.0
Time Frame
From baseline
Title
Immune response
Time Frame
From baseline
Secondary Outcome Measure Information:
Title
Impact of dose on immunologic response
Time Frame
From baseline to month 15
Title
Persistence of DNA at the injection site
Time Frame
At 1 and 6 months after last vaccination
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary L. Disis
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
36326756
Citation
Disis MLN, Guthrie KA, Liu Y, Coveler AL, Higgins DM, Childs JS, Dang Y, Salazar LG. Safety and Outcomes of a Plasmid DNA Vaccine Encoding the ERBB2 Intracellular Domain in Patients With Advanced-Stage ERBB2-Positive Breast Cancer: A Phase 1 Nonrandomized Clinical Trial. JAMA Oncol. 2023 Jan 1;9(1):71-78. doi: 10.1001/jamaoncol.2022.5143.
Results Reference
derived
Learn more about this trial
Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer
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