search
Back to results

Vaccine Therapy in Treating Patients With Stage IV HLA-A2 and HER2 Positive Breast or Ovarian Cancer Receiving Trastuzumab

Primary Purpose

HER2/Neu Positive, HLA-A2 Positive Cells Present, Stage IV Breast Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HER-2/neu Peptide Vaccine
Laboratory Biomarker Analysis
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HER2/Neu Positive

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Subjects must have either stage IV breast or ovarian cancer in remission or with stable disease on trastuzumab monotherapy HER2 overexpression by immunohistocytochemistry (IHC) of 2+ or 3+, in the primary tumor or metastasis; if overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by fluorescence in situ hybridization (FISH) Subjects must be HLA-A2 positive Eligible subjects must have completed appropriate treatment for their primary disease and be off cytotoxic chemotherapy and any immunosuppressive agents such as systemic steroids for at least 30 days prior to enrollment; patients should continue trastuzumab monotherapy throughout the course of this protocol; concurrent hormonal and biphosphonate therapies are allowed Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score = 0 or 1 Male subjects must agree to contraceptive use during the study period (7 months) and non-menopausal female subjects must agree to contraception for the remainder of their childbearing years Hematocrit >= 30 performed within 60 days of enrollment Platelet count >= 100,000 performed within 60 days of enrollment White blood cells (WBC) >= 3000/ul performed within 60 days of enrollment Stable creatinine =< 2.0 mg/dL or creatinine clearance >= 60 ml/min performed within 60 days of enrollment Serum bilirubin < 1.5 mg/dl performed within 60 days of enrollment Serum glutamic-oxaloacetic transaminase (SGOT) < 2 x upper limit of normal (ULN) performed within 60 days of enrollment 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 Patients must have a baseline left ventricular ejection fraction (LVEF) measured by multi-gated acquisition scan (MUGA) equal to or greater than the lower limit of normal for the radiology facility and if there are two consecutive MUGAS performed while on trastuzumab from the same radiology facility, there cannot be a decrease in LVEF of > 15% from the original MUGA scan Exclusion Criteria: Subjects cannot be simultaneously enrolled on other treatment studies Any contraindication to receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) based vaccine products Cardiac disease, specifically restrictive cardiomyopathy, unstable angina within the last 6 months prior to enrollment, New York Heart Association functional class III-IV heart failure on active treatment with normalized LVEF on therapy, and symptomatic pericardial effusion Active autoimmune disease Subjects cannot have an active immunodeficiency disorder, e.g. human immunodeficiency virus (HIV)

Sites / Locations

  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (HER-2/neu peptide vaccine)

Arm Description

Patients receive HER-2/neu peptide vaccine ID once per month for 6 months in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Immune Response Measured by IFN-gamma Secreting PBMC Precursor Frequency by ELIspot and HLA-A2 Major Histocompatibility Complex Tetramer Analysis
ELIspot: Increased immune response is defined as spots per well (SPW) greater than 2 standard deviations (SD) above baseline value, remained the same if the mean SPW was within 2 SD of the previous value, or decreased if the mean SPW was greater than 2 SD below the previous value. Two SD is equivalent to a P value of .05 in that there is a 95% probability that the values are statistically significant. T is reported as percentage of patients and their corresponding results. HLA-A2 Major Histocompatibility Complex Tetramer Analysis is evaluated using a non-radioactive assay for cell lysis. The HLA-A2 transfected human HER2/neu expressing breast cancer cell line, SKBR3-A2 T cells, expanded after stimulation with immunizing peptide, were added in an effector/target ratio of 40:1. Percent specific lysis was calculated as: ([experimental release-spontaneous releases of cytotoxic T-lymphocyte cells and target cells]/[maximum release-spontaneous release of target cells])X100.
Number of Adverse Events Graded Using National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0
Descriptive statistics will be used to summarize changes from baseline. At the point the participant signs consent and before they start vaccine we record their existing baseline events (symptoms and diagnoses) and assign a grade to them (see below). Once a participant starts vaccine treatment adverse event AEs were recorded if they are new to the participant or if they increased in severity over their baseline. Grade refers to the severity of the AE. The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Secondary Outcome Measures

Overall Survival
Survival for the Stage IV breast cancer patients will be compared to historical control.

Full Information

First Posted
September 13, 2005
Last Updated
May 31, 2023
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00194714
Brief Title
Vaccine Therapy in Treating Patients With Stage IV HLA-A2 and HER2 Positive Breast or Ovarian Cancer Receiving Trastuzumab
Official Title
Phase I/II Study of Combination Immunotherapy for the Generation of HER-2/Neu (HER2) Specific Cytotoxic T Cells (CTL) in Vivo
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
March 31, 2021 (Actual)
Study Completion Date
May 22, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase I/II trial studies the side effects of vaccine therapy and to see how well it works in treating patients with stage IV major histocompatibility complex, class I, A2 antigen (HLA-A2) and human epidermal growth factor receptor 2 (HER2) positive breast or ovarian cancer who are receiving trastuzumab. Giving booster vaccines made from HER2 peptides may help increase HER2 specific immunity and immune memory cells.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the safety of administering a HER2 cytotoxic T-cell (CTL) peptide-based vaccine (HER-2/neu peptide vaccine) to stage IV breast and ovarian cancer patients receiving maintenance trastuzumab. II. To quantify and characterize antigen specific T cell subsets specific to HER2 in peripheral blood mononuclear cell (PBMC) of patients after vaccination with a HER2 CTL peptide-based vaccine while receiving maintenance trastuzumab. SECONDARY OBJECTIVES: I. To evaluate overall survival (OS) in patients who complete a vaccination series with a HER2 CTL peptide-based vaccine while receiving maintenance trastuzumab. OUTLINE: Patients receive HER-2/neu peptide vaccine intradermally (ID) once per month for 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months, and then yearly for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2/Neu Positive, HLA-A2 Positive Cells Present, Stage IV Breast Cancer, Stage IV Ovarian Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (HER-2/neu peptide vaccine)
Arm Type
Experimental
Arm Description
Patients receive HER-2/neu peptide vaccine ID once per month for 6 months in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
HER-2/neu Peptide Vaccine
Other Intervention Name(s)
HER-2-Neu Peptide Vaccine, HER-2/neu Helper-Peptide Vaccine
Intervention Description
Given ID
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Immune Response Measured by IFN-gamma Secreting PBMC Precursor Frequency by ELIspot and HLA-A2 Major Histocompatibility Complex Tetramer Analysis
Description
ELIspot: Increased immune response is defined as spots per well (SPW) greater than 2 standard deviations (SD) above baseline value, remained the same if the mean SPW was within 2 SD of the previous value, or decreased if the mean SPW was greater than 2 SD below the previous value. Two SD is equivalent to a P value of .05 in that there is a 95% probability that the values are statistically significant. T is reported as percentage of patients and their corresponding results. HLA-A2 Major Histocompatibility Complex Tetramer Analysis is evaluated using a non-radioactive assay for cell lysis. The HLA-A2 transfected human HER2/neu expressing breast cancer cell line, SKBR3-A2 T cells, expanded after stimulation with immunizing peptide, were added in an effector/target ratio of 40:1. Percent specific lysis was calculated as: ([experimental release-spontaneous releases of cytotoxic T-lymphocyte cells and target cells]/[maximum release-spontaneous release of target cells])X100.
Time Frame
Up to 1.5 years (12 months following the last vaccination)
Title
Number of Adverse Events Graded Using National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0
Description
Descriptive statistics will be used to summarize changes from baseline. At the point the participant signs consent and before they start vaccine we record their existing baseline events (symptoms and diagnoses) and assign a grade to them (see below). Once a participant starts vaccine treatment adverse event AEs were recorded if they are new to the participant or if they increased in severity over their baseline. Grade refers to the severity of the AE. The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Time Frame
Up to 7 months (30 days following the last vaccination)
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Survival for the Stage IV breast cancer patients will be compared to historical control.
Time Frame
Up to 5 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must have either stage IV breast or ovarian cancer in remission or with stable disease on trastuzumab monotherapy HER2 overexpression by immunohistocytochemistry (IHC) of 2+ or 3+, in the primary tumor or metastasis; if overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by fluorescence in situ hybridization (FISH) Subjects must be HLA-A2 positive Eligible subjects must have completed appropriate treatment for their primary disease and be off cytotoxic chemotherapy and any immunosuppressive agents such as systemic steroids for at least 30 days prior to enrollment; patients should continue trastuzumab monotherapy throughout the course of this protocol; concurrent hormonal and biphosphonate therapies are allowed Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score = 0 or 1 Male subjects must agree to contraceptive use during the study period (7 months) and non-menopausal female subjects must agree to contraception for the remainder of their childbearing years Hematocrit >= 30 performed within 60 days of enrollment Platelet count >= 100,000 performed within 60 days of enrollment White blood cells (WBC) >= 3000/ul performed within 60 days of enrollment Stable creatinine =< 2.0 mg/dL or creatinine clearance >= 60 ml/min performed within 60 days of enrollment Serum bilirubin < 1.5 mg/dl performed within 60 days of enrollment Serum glutamic-oxaloacetic transaminase (SGOT) < 2 x upper limit of normal (ULN) performed within 60 days of enrollment 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 Patients must have a baseline left ventricular ejection fraction (LVEF) measured by multi-gated acquisition scan (MUGA) equal to or greater than the lower limit of normal for the radiology facility and if there are two consecutive MUGAS performed while on trastuzumab from the same radiology facility, there cannot be a decrease in LVEF of > 15% from the original MUGA scan Exclusion Criteria: Subjects cannot be simultaneously enrolled on other treatment studies Any contraindication to receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) based vaccine products Cardiac disease, specifically restrictive cardiomyopathy, unstable angina within the last 6 months prior to enrollment, New York Heart Association functional class III-IV heart failure on active treatment with normalized LVEF on therapy, and symptomatic pericardial effusion Active autoimmune disease Subjects cannot have an active immunodeficiency disorder, e.g. human immunodeficiency virus (HIV)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary Disis
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19720923
Citation
Disis ML, Wallace DR, Gooley TA, Dang Y, Slota M, Lu H, Coveler AL, Childs JS, Higgins DM, Fintak PA, dela Rosa C, Tietje K, Link J, Waisman J, Salazar LG. Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. J Clin Oncol. 2009 Oct 1;27(28):4685-92. doi: 10.1200/JCO.2008.20.6789. Epub 2009 Aug 31.
Results Reference
derived
Links:
URL
http://depts.washington.edu/tumorvac/
Description
Tumor Vaccine Group, University of Washington

Learn more about this trial

Vaccine Therapy in Treating Patients With Stage IV HLA-A2 and HER2 Positive Breast or Ovarian Cancer Receiving Trastuzumab

We'll reach out to this number within 24 hrs