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

Phase I/II Study of Combination Immunotherapy for the Generation of HER-2/Neu (HER2) Specific Cytotoxic T Cells (CTL) in Vivo

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.

Study Overview

• Status: Completed
• Conditions: Stage IV Breast Cancer; HER2/Neu Positive; HLA-A2 Positive Cells Present; Stage IV Ovarian Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: HER-2/neu Peptide Vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: HER-2/neu Peptide Vaccine; Given ID; Other Names: HER-2-Neu Peptide Vaccine; HER-2/neu Helper-Peptide Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 1.5 years (12 months following the last vaccination)
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	Up to 7 months (30 days following the last vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Survival for the Stage IV breast cancer patients will be compared to historical control.	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mary Disis, Fred Hutch/University of Washington Cancer Consortium

Publications and helpful links

General Publications

• 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.

Helpful Links

• Tumor Vaccine Group, University of Washington

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): May 22, 2023

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimated): September 19, 2005

Study Record Updates

• Last Update Posted (Estimated): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 6304 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); NCI-2016-00895 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RG1000607 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)