Clinical Trials /

Safety and Immune Response to a Mammaglobin-A DNA Vaccine In Breast Cancer Patients Undergoing Neoadjuvant Endocrine Therapy

NCT02204098

Description:

The purpose of this research study is to find out about the safety of injecting the gene (DNA) for mammaglobin-A into people with breast cancer. The DNA used in this study was purified from bacteria and contains the gene for mammaglobin-A. Mammaglobin-A is a protein that is highly expressed by breast cancer cells. Injection of mammaglobin-A DNA may be a way to generate an immune response to breast cancer cells. There is evidence that an immune response may be a way to fight cancer. In addition to evaluating the safety of the mammaglobin-A injection, this study is also looking at the immune response that the participant's body has after each injection.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Safety and Immune Response to a Mammaglobin-A DNA Vaccine In <span class="go-doc-concept go-doc-disease">Breast Cancer</span> Patients Undergoing Neoadjuvant <span class="go-doc-concept go-doc-intervention">Endocrine Therapy</span>

Title

  • Brief Title: Safety and Immune Response to a Mammaglobin-A DNA Vaccine In Breast Cancer Patients Undergoing Neoadjuvant Endocrine Therapy
  • Official Title: A Phase 1B Randomized Clinical Trial to Evaluate the Safety and Immune Response to a Mammaglobin-A DNA Vaccine in Breast Cancer Patients Undergoing Neoadjuvant Endocrine Therapy
  • Clinical Trial IDs

    NCT ID: NCT02204098

    ORG ID: 201407100

    Trial Conditions

    Breast Cancer

    Breast Carcinoma

    Malignant Neoplasm of Breast

    Trial Interventions

    Drug Synonyms Arms
    Anastrozole Arimidex Arm 1: Endocrine Therapy & Mammaglobin-A DNA Vaccine, Arm 2 - Endocrine Therapy Only
    Letrozole Femara Arm 1: Endocrine Therapy & Mammaglobin-A DNA Vaccine, Arm 2 - Endocrine Therapy Only
    Tamoxifen Nolvadex, Apo-Tamox, Clonoxifen, Dignotamoxi, Ebefen, Emblon, Estroxyn, Fentamox, Genox, Gen-Tamoxifen, Jenoxifen, Kessar, Ledertam, Lesporene, Nolgen, Noltam, Nolvadex-D, Nourytam, Novofen, Novo-Tamoxifen, Oestrifen, Oncotam, PMS-Tamoxifen, Soltamox, Tamax, Tamaxin, Tamifen, Tamizam, Tamofen, Tamoxasta, Zemide Arm 1: Endocrine Therapy & Mammaglobin-A DNA Vaccine, Arm 2 - Endocrine Therapy Only
    Exemestane Aromasin Arm 1: Endocrine Therapy & Mammaglobin-A DNA Vaccine, Arm 2 - Endocrine Therapy Only
    Goserelin Zoladex Arm 1: Endocrine Therapy & Mammaglobin-A DNA Vaccine, Arm 2 - Endocrine Therapy Only

    Trial Purpose

    The purpose of this research study is to find out about the safety of injecting the gene
    (DNA) for mammaglobin-A into people with breast cancer. The DNA used in this study was
    purified from bacteria and contains the gene for mammaglobin-A. Mammaglobin-A is a protein
    that is highly expressed by breast cancer cells. Injection of mammaglobin-A DNA may be a way
    to generate an immune response to breast cancer cells. There is evidence that an immune
    response may be a way to fight cancer. In addition to evaluating the safety of the
    mammaglobin-A injection, this study is also looking at the immune response that the
    participant's body has after each injection.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm 1: Endocrine Therapy & Mammaglobin-A DNA Vaccine Experimental Participants will be treated with neoadjuvant endocrine therapy, with the dose and agent to be determined by the treating physician The schedule of vaccination is day 28 7, day 56 7 and day 84 7 with at least 21 days between injection days. All study injections will be given intramuscularly using an integrated electroporation administration system. At each vaccination timepoint, patients will receive two injections of the mammaglobin-A DNA vaccine, one injection into each deltoid or lateralis. Anastrozole, Letrozole, Tamoxifen, Exemestane, Goserelin
    Arm 2 - Endocrine Therapy Only Active Comparator Participants will be treated with neoadjuvant endocrine therapy, with the dose and agent to be determined by the treating physician. Anastrozole, Letrozole, Tamoxifen, Exemestane, Goserelin

    Eligibility Criteria

    Inclusion Criteria:

    A patient will be eligible for inclusion in this study only if ALL of the following
    criteria apply:

    - Newly diagnosed histologically confirmed invasive breast cancer.

    - Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2- (0 or 1+ by
    IHC or FISH negative for amplification) breast cancer by AJCC 7th edition clinical
    staging, with the goal being surgery to completely excise the tumor in the breast and
    the lymph node. If the patient has invasive cancer in the contralateral breast, the
    patient is not eligible for this study.

    - At least 1 measurable lesion that is palpable and which can be measured by
    bi-dimensional tape, ruler, or caliper technique. The minimum size of the largest
    tumor diameter is at least 2.0 cm by imaging or physical examination.

    - Candidate for neoadjuvant endocrine therapy.

    - At least 18 years of age.

    - Eastern Cooperative Oncology Group (ECOG) performance status 2.

    - Adequate organ and marrow function no more than 14 days prior to registration as
    defined below:

    - WBC 3,000/L

    - absolute neutrophil count 1,500/L

    - platelets 100,000/L

    - total bilirubin institutional upper limit of normal

    - AST/ALT 2.5 X institutional upper limit of normal

    - creatinine institutional upper limit of normal OR creatinine clearance 60
    mL/min/1.73 m2 for patients with creatinine above IULN

    - Postmenopausal or premenopausal. NOTE: Postmenopausal women, verified by: (1)
    bilateral surgical oophorectomy, or (2) no spontaneous menses 1 year or (3) no
    menses for <1 year with FSH and estradiol levels in postmenopausal range, according
    to institutional standards. Premenopausal women, verified by: (1) regular menses, or
    (2) FSH and estradiol levels in premenopausal range, according to institutional
    standards.

    - Able to understand, and willing to sign a written informed consent document.

    - A patient will be eligible for randomization only if both of the following criteria
    apply:

    - Confirmation that primary tumor expresses mammaglobin-A by IHC.

    - Tumor Ki67 value is 10% after 14 days of endocrine therapy.

    Exclusion Criteria:

    A patient will be ineligible for inclusion in this study if ANY of the following criteria
    apply:

    - Received any of the following for treatment of this cancer:

    - Surgery

    - Radiation therapy

    - Chemotherapy

    - Biotherapy

    - Hormonal therapy

    - Investigational agent

    - Receiving any other investigational agent(s) or has received an investigational agent
    within the last 30 days.

    - Known metastatic disease.

    - Known allergy, or history of serious adverse reaction to vaccines such as
    anaphylaxis, hives, or respiratory difficulty.

    - Prior axillary lymph node sampling (sentinel lymph node biopsy or axillary lymph node
    dissection). FNA of axillary lymph node is acceptable.

    - Invasive cancer in the contralateral breast.

    - Uncontrolled intercurrent illness including, but not limited to ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia, or psychiatric illness/social situation that would limit compliance with
    study requirements.

    - Prior or currently active autoimmune disease requiring management with
    immunosuppression. This includes inflammatory bowel disease, ulcerative colitis,
    Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis,
    hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic
    lupus erythematosus, Sjorgen's syndrome, sarcoidosis, or other rheumatologic disease
    or any other medical condition or use of medication (e.g., corticosteroids) which
    might make it difficult for the patient to complete the full course of treatments or
    to generate an immune response to vaccines. Asthma or chronic obstructive pulmonary
    disease that does not require daily systemic corticosteroids is acceptable. Any
    patients receiving steroids should be discussed with the PI to determine if eligible.

    - Pregnant or breastfeeding. A negative serum or pregnancy test is required no more
    than 7 days before study entry, and patients must be willing to employ adequate
    contraception. Women of childbearing potential must use two forms of contraception
    (hormonal or barrier method of birth control; abstinence) prior to study entry and
    for the duration of study participation.

    - Known HIV-positive status. These patients are ineligible because of the potential
    inability to generate an immune response to vaccines.

    - Subjects with a strong likelihood of non-adherence such as difficulties in adhering
    to follow-up schedule due to geographic distance from the Siteman Cancer Center
    should not knowingly be registered.

    - Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue
    for the eligible injection sites (left and right medial deltoid region) exceeds 40 mm

    - Individuals in whom the ability to observe possible local reactions at the eligible
    injection sites (deltoid region) is, in the opinion of the investigator, unacceptably
    obscured due to a physical condition or permanent body art

    - Therapeutic or traumatic metal implant in the skin or muscle of either deltoid
    region.

    - Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or
    hepatic or renal functional abnormality as determined by the investigator based on
    medical history, physical examination, EKG, and/or laboratory screening test

    - Any chronic or active neurologic disorder, including seizures and epilepsy, excluding
    a single febrile seizure as a child

    - Syncopal episode within 12 months of screening

    - Current use of any electronic stimulation device, such as cardiac demand pacemakers,
    automatic implantable cardiac defibrillator, nerve stimulators, or deep brain
    stimulators.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Safety

    Secondary Outcome Measures

    Immune response

    Trial Keywords