Clinical Trials /

Vaccine Therapy in Preventing Cancer Recurrence in Patients With Non-Metastatic, Node Positive, HER2 Negative Breast Cancer That is in Remission

NCT02780401

Description:

This phase I trial studies the side effects and best dose of a vaccine therapy in preventing cancer from coming back in patients with non-metastatic, node positive, human epidermal growth factor receptor (HER)2 negative breast cancer in which all signs and symptoms have disappeared. Vaccines made from deoxyribonucleic acid (DNA) may help the body build an effective immune response to kill tumor cells. Giving multiple vaccinations may make a stronger immune response and prevent or delay the return of cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Vaccine Therapy in Preventing Cancer Recurrence in Patients With Non-Metastatic, Node Positive, <span class="go-doc-concept go-doc-alteration">HER2 Negative</span> Breast Cancer That is in Remission

Title

  • Brief Title: Vaccine Therapy in Preventing Cancer Recurrence in Patients With Non-Metastatic, Node Positive, HER2 Negative Breast Cancer That is in Remission
  • Official Title: A Phase I Trial of the Safety and Immunogenicity of a DNA Plasmid Based Vaccine (WOKVAC) Encoding Epitopes Derived From Three Breast Cancer Antigens (IGFBP-2, HER2, and IGF-IR) in Patients With Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02780401

    ORG ID: 9626

    NCI ID: NCI-2016-00581

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This phase I trial studies the side effects and best dose of a vaccine therapy in preventing
    cancer from coming back in patients with non-metastatic, node positive, human epidermal
    growth factor receptor (HER)2 negative breast cancer in which all signs and symptoms have
    disappeared. Vaccines made from deoxyribonucleic acid (DNA) may help the body build an
    effective immune response to kill tumor cells. Giving multiple vaccinations may make a
    stronger immune response and prevent or delay the return of cancer.

    Detailed Description

    PRIMARY OBJECTIVES:

    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.

    SECONDARY OBJECTIVES:

    I. To determine the immunogenicity of pUMVC3-IGFBP2-HER2-IGF1R (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 changes in mammographic density using clinically available images prior to
    Baseline and post vaccination as an exploratory analysis.

    V. To determine a recommended phase 2 WOKVAC dose for further breast cancer prevention
    studies.

    OUTLINE: This is a dose escalation study of WOKVAC. Patients receive WOKVAC with
    sargramostim intradermally (ID) on day 1. Courses repeat every 28 days for up to 3 courses
    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 up to 5 years thereafter.

    Trial Arms

    Name Type Description Interventions
    Treatment (WOKVAC with sargramostim) Experimental Patients receive WOKVAC with sargramostim ID on day 1. Courses repeat every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with 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.

    Eligibility Criteria

    Inclusion Criteria:

    - 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 < 3+ HER2 expression by
    immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) negative
    as confirmed by the patient's existing pathology report

    - Patients must be at least 28 days post cytotoxic chemotherapy and/or radiotherapy,
    monoclonal antibody and/or other biologic therapy, prior to enrollment; patients on
    bisphosphonates, denosumab, and/or endocrine therapy 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

    - Hemoglobin (Hgb) >= 10 g/dl

    - Lymphocyte count >= 800/mm^3

    - Platelet count >= 75,000/mm^3

    - Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min

    - Total bilirubin =< 1.5 mg/dl

    - Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) =< 2
    times upper limit of normal (ULN)

    - Blood glucose =< ULN for the performing laboratory

    - 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

    - 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

    - Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:

    - 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; 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of toxicity assessed by adverse events per Common Terminology Criteria for Adverse Events version 4.0

    Secondary Outcome Measures

    Assessment of the immunogenicity of WOKVAC by generation of IGFBP-2, HER2, and IGF-1R specific type 1 (Th1) T- cells

    Assessment of T helper Th1:Th2 ratio

    Assessment of immunoglobulin (Ig)G antibodies

    Level of antigen specific central and effector memory phenotypes (Persistent memory T cell response)

    Modulation of T regulatory cell (Tregs) levels

    Modulation of myeloid derived suppressor cell (MDSC) levels

    Trial Keywords

    Stage I

    Stage II

    Stage III

    HER2/Neu Negative

    Axillary Nodes

    Vaccine Therapy