Vaccine Therapy in Preventing Cancer Recurrence in Patients with Non-Metastatic, Node Positive, HER2 Negative Breast Cancer That is in Remission
- Patients with non-metastatic, node positive, HER2 negative breast cancer, confirmed by pathology report, who are in remission and defined as having no evidence of disease (NED); HER2 negative is defined as * 0-1+ HER2 expression by immunohistochemistry (IHC) OR * Fluorescence in situ hybridization (FISH) negative OR * HER2 2+ and FISH negative
- Patients must be at least 28 days post cytotoxic chemotherapy, radiotherapy, monoclonal antibody and/or other biologic therapy, prior to enrollment; patients on bisphosphonates, denosumab, and/or endocrine therapy administered during the study are eligible and may continue throughout duration of study
- Patients must be at least 28 days post systemic steroids prior to enrollment
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score of =< 2
- White blood cell (WBC) >= 3000/mm^3 (within 90 days of enrollment)
- Hemoglobin (Hgb) >= 10 g/dl (within 90 days of enrollment)
- Lymphocyte count >= 800/mm^3 (within 90 days of enrollment)
- Platelet count >= 75,000/mm^3 (within 90 days of enrollment)
- Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min (within 90 days of enrollment)
- Total bilirubin =< 1.5 mg/dl (within 90 days of enrollment)
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 2 times upper limit of normal (ULN) (within 90 days of enrollment)
- Glycosylated hemoglobin measurement (HbA1c) < 5.7% (within 90 days of enrollment)
- Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment
- The effects of WOKVAC on the developing human fetus are unknown; for this reason, patients who are having sex that can lead to pregnancy must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) for the duration of study participation; should a woman become pregnant while participating in the study, she should inform her study doctor immediately and will not receive any more study treatment
- Left ventricular ejection fraction (LVEF) results must be >= lower limit of normal (LLN) for institution performing based on results from the multi-gated acquisition (MUGA) or echocardiogram (ECHO) done at baseline
- Willing to not undergo any elective surgical procedure with general anesthesia or conscious sedation through the 1 month post-vaccination visit
- Ability to understand and the willingness to sign a written informed consent document
- Patients with any of the following cardiac conditions: * Symptomatic restrictive cardiomyopathy * Dilated cardiomyopathy * Unstable angina within 4 months prior to enrollment * New York Heart Association functional class III-IV heart failure on active treatment * Symptomatic pericardial effusion
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to WOKVAC
- Patients with any contraindication or known hypersensitivity to receiving sargramostatin (recombinant human granulocyte macrophage colony stimulating factor [rhuGM-CSF]) or other yeast based products
- Pregnant women are excluded from this study because WOKVAC is a vaccine agent with unknown potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with WOKVAC, breastfeeding should be discontinued if the mother is treated with this vaccine
- History of diabetes
- Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
- History of autoimmunity that has not been controlled with treatment in the last 12 months
I. To assess the safety of 3 escalating doses of a deoxyribonucleic acid (DNA) plasmid based vaccine encoding three breast cancer antigens (insulin-like growth factor-binding protein [IGFBP]-2, HER2, and insulin-like growth factor [IGF]-1 receptor [1R]) in patients with breast cancer.
I. To determine the immunogenicity of pUMVC3-IGFBP2-HER2-IGF1R plasmid DNA vaccine (WOKVAC) T helper cells (Th) polyepitope plasmid based vaccine in patients with breast cancer at 3 escalating doses.
II. To determine whether a WOKVAC Th polyepitope plasmid based vaccine elicits a persistent memory T cell response.
III. To evaluate whether WOKVAC vaccination modulates T regulatory cells (Treg) and myeloid derived suppressor cells (MDSC).
IV. To evaluate antibody immunity to further define Th2 immune response.
V. To determine a recommended phase 2 WOKVAC dose for further breast cancer prevention studies.
VI. To assess the long-term effects of 3 escalating doses of a deoxyribonucleic acid (DNA) plasmid based vaccine encoding three breast cancer antigens (IGFBP-2, HER2, and IGF-1R) in patients with breast cancer, for 5 years from enrollment to satisfy the evaluation requirements for the Food and Drug Administration (FDA).
OUTLINE: This is a dose escalation study.
Patients receive pUMVC3-IGFBP2-HER2-IGF1R plasmid DNA vaccine with sargramostim intradermally (ID) on day 1. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Patients with axillary lymph node dissection (ALND) will have vaccine administered to the contralateral arm. Patients with bilateral ALND will have vaccine administered in the thigh. As much as possible each vaccine dose will be given within the same draining lymph node site. Patients will be monitored for a minimum of 60 minutes post vaccine administration.
After completion of study treatment, patients are followed up at 1 month, 6 months and annually for up to 5 years thereafter.
Trial Phase Phase I
Trial Type Prevention
University of Wisconsin Hospital and Clinics
Mary Lenora (Nora) Disis
- Primary ID UWI4090
- Secondary IDs NCI-2016-00581, UWI2014-03-01, 9626, N01-CN-2012-00033
- Clinicaltrials.gov ID NCT02780401