Clinical Trials /

Vaccine Therapy in Treating Patients With HER2-Negative Stage III-IV Breast Cancer

NCT02157051

Description:

This phase I trial studies the side effects and best dose of multiantigen deoxyribonucleic acid (DNA) plasmid-based vaccine in treating patients with human epidermal growth factor receptor 2 (HER2)-negative stage III-IV breast cancer. Multiantigen DNA plasmid-based vaccine may target immunogenic proteins expressed in breast cancer stem cells which are the component of breast cancer that is resistant to chemotherapy and has the ability to spread. Vaccines made from DNA may help the body build an effective immune response to kill tumor cells.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Vaccine Therapy in Treating Patients With <span class="go-doc-concept go-doc-biomarker">HER2</span>-Negative Stage III-IV <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Vaccine Therapy in Treating Patients With HER2-Negative Stage III-IV Breast Cancer
  • Official Title: A Phase I Trial of the Safety and Immunogenicity of a Multiple Antigen Vaccine (STEMVAC) in HER2 Negative Advanced Stage Breast Cancer Patients
  • Clinical Trial IDs

    NCT ID: NCT02157051

    ORG ID: 9140

    NCI ID: NCI-2014-01070

    Trial Conditions

    HER2/Neu Negative

    Recurrent Breast Carcinoma

    Stage IIIA Breast Cancer

    Stage IIIB Breast Cancer

    Stage IIIC Breast Cancer

    Stage IV Breast Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This phase I trial studies the side effects and best dose of multiantigen deoxyribonucleic
    acid (DNA) plasmid-based vaccine in treating patients with human epidermal growth factor
    receptor 2 (HER2)-negative stage III-IV breast cancer. Multiantigen DNA plasmid-based
    vaccine may target immunogenic proteins expressed in breast cancer stem cells which are the
    component of breast cancer that is resistant to chemotherapy and has the ability to spread.
    Vaccines made from DNA may help the body build an effective immune response to kill tumor
    cells.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the safety of intradermal administration of up to 3 escalating doses of
    CD105/Yb-1/SOX2 CDH3/MDM2 multiplasmid vaccine (STEMVAC) in patients with HER2-negative
    advanced stage breast cancer.

    II. To determine the most immunogenic dose of STEMVAC in patients with HER2-negative
    advanced stage breast cancer.

    SECONDARY OBJECTIVES:

    I. To determine whether a STEMVAC T helper 1 cells (Th1) polyepitope plasmid based vaccine
    elicits a persistent memory T cell response and whether immunity can be further
    enhanced/maintained by two additional STEMVAC vaccines (boosters) given 3 and 9 months after
    the priming regimen.

    II. To evaluate whether STEMVAC vaccination modulates T regulatory cells and myeloid-derived
    suppressor cells (MDSC).

    OUTLINE: This is a dose-escalation study.

    Patients receive CD105/Yb-1/SOX2/CDH3/MDM2 polyepitope multiplasmid DNA vaccine with
    recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) intradermally
    (ID) every 28 days for 3 months and booster vaccines at 6 and 12 months in the absence of
    disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up twice yearly for 5 years.

    Trial Arms

    Name Type Description Interventions
    Treatment (STEMVAC) Experimental Patients receive CD105/Yb-1/SOX2/CDH3/MDM2 polyepitope multiplasmid DNA vaccine with rhuGM-CSF ID every 28 days for 3 months and booster vaccines at 6 and 12 months in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

    Inclusion Criteria:

    - Patients with stage III-IV HER2 negative breast cancer treated with primary or
    salvage therapy and now have:

    - No evidence of disease (NED), or

    - Stable bone only disease

    - Patients who have completed standard of care and recovered with mild to no residual
    toxicity from recent therapy

    - Patients must be at least 28 days post cytotoxic chemotherapy, and/or monoclonal
    antibody therapy, prior to enrollment

    - Patients must be at least 28 days post systemic steroids prior to enrollment

    - Patients on bisphosphonates and/or endocrine therapy are eligible

    - Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score
    of =< 1

    - 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

    - Estimated life expectancy of more than 6 months

    - White blood cells (WBC) >= 3000/mm^3

    - Hemoglobin (Hgb) >= 10 mg/dl

    - Serum creatinine =< 1.2 mg/dl when adjusted for body surface area (BSA) 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 < 1.5 ULN

    - Postmenopausal women determined by one of the following:

    - Bilateral surgical oophorectomy

    - Age greater than or equal 60 years

    - Age < 60 years, with amenorrhea greater than or equal to 12 months and
    follicle-stimulating hormone within postmenopausal range

    - Non-menopausal female patients who are having sex that can lead to pregnancy must
    agree to contraception for the duration of study

    - Male patients who are having sex that can lead to pregnancy must use an acceptable
    form of contraception throughout the course of the study

    Exclusion Criteria:

    - Patients with any of the following cardiac conditions:

    - Symptomatic restrictive 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 at risk for gastrointestinal bleeding (example: peptic ulcer disease,
    prolonged daily non-steroidal anti-inflammatory use)

    - Patients with any seizure disorder

    - Patients with any contraindication to receiving rhuGM-CSF based products

    - Patients with any clinically significant autoimmune disease uncontrolled with
    treatment

    - Patients who are simultaneously enrolled in any other treatment study

    - Patients who are pregnant or breastfeeding

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Immunologic efficacy defined as achievement of a statistically significant increase in Th1 cell immunity for at least 50% of the immunizing antigens as compared to baseline

    Incidence of toxicity per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 4.0

    Secondary Outcome Measures

    Memory Th1 dominant immune response to all five antigens over time

    Modulation of MDSC with vaccination

    Modulation of T-regulatory (Treg) cells with vaccination

    Trial Keywords