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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT00194714
First received: September 13, 2005
Last updated: August 26, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
HER2/Neu Positive
HLA-A2 Positive Cells Present
Stage IV Breast Cancer
Stage IV Ovarian Cancer
Biological: HER-2/neu Peptide Vaccine
Other: Laboratory Biomarker Analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Combination Immunotherapy for the Generation of HER-2/Neu (HER2) Specific Cytotoxic T Cells (CTL) in Vivo

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Immune response measured by cytokine flow cytometry (CFC) and HLA-A2 major histocompatibility complex tetramer analysis [ Time Frame: Up to 1.5 years (12 months following the last vaccination) ] [ Designated as safety issue: No ]
    Defined as either the development of, in patients with no measurable precursors at baseline, precursor frequencies > 1:20,000 as measured by CFC; or as a 2-fold increase in baseline precursor frequency in those patients who have a pre existent immune response.

  • Incidence of adverse events graded using National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 [ Time Frame: Up to 7 months (30 days following the last vaccination) ] [ Designated as safety issue: Yes ]
    Descriptive statistics will be used to summarize changes from baseline.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Survival for the Stage IV breast cancer patients will be compared to historical control.


Estimated Enrollment: 20
Study Start Date: May 2016
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (HER-2/neu peptide vaccine)
Patients receive HER-2/neu peptide vaccine ID once per month for 6 months in the absence of disease progression or unacceptable toxicity.
Biological: HER-2/neu Peptide Vaccine
Given ID
Other Names:
  • HER-2-Neu Peptide Vaccine
  • HER-2/neu Helper-Peptide Vaccine
Other: Laboratory Biomarker Analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00194714

Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mary Disis Fred Hutch/University of Washington Cancer Consortium
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT00194714     History of Changes
Other Study ID Numbers: 6304  NCI-2016-00895  6304  P30CA015704 
Study First Received: September 13, 2005
Last Updated: August 26, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 08, 2016