Clinical Trials /

Safety and Immunogenicity of a Personalized Polyepitope DNA Vaccine Strategy in Breast Cancer Patients With Persistent Triple-Negative Disease Following Neoadjuvant Chemotherapy

NCT02348320

Description:

This is a phase 1 open-label study to evaluate the safety and immunogenicity of a personalized polyepitope DNA vaccine strategy. The personalized polyepitope DNA vaccines will be formulated as naked plasmid DNA vaccines. The hypothesis of this study is that personalized polyepitope DNA vaccines will be safe for human administration and capable of generating measurable CD8 T cell responses to mutant tumor-specific antigens.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Safety and Immunogenicity of a Personalized Polyepitope DNA Vaccine Strategy in <span class="go-doc-concept go-doc-disease">Breast Cancer</span> Patients With Persistent Triple-Negative Disease Following <span class="go-doc-concept go-doc-intervention">Neoadjuvant Chemotherapy</span>

Title

  • Brief Title: Safety and Immunogenicity of a Personalized Polyepitope DNA Vaccine Strategy in Breast Cancer Patients With Persistent Triple-Negative Disease Following Neoadjuvant Chemotherapy
  • Official Title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Personalized Polyepitope DNA Vaccine Strategy in Breast Cancer Patients With Persistent Triple-Negative Disease Following Neoadjuvant Chemotherapy
  • Clinical Trial IDs

    NCT ID: NCT02348320

    ORG ID: 201505074

    Trial Conditions

    Triple Negative Breast Cancer

    Triple-Negative Breast Cancer

    Triple Negative Breast Neoplasms

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This is a phase 1 open-label study to evaluate the safety and immunogenicity of a
    personalized polyepitope DNA vaccine strategy. The personalized polyepitope DNA vaccines
    will be formulated as naked plasmid DNA vaccines. The hypothesis of this study is that
    personalized polyepitope DNA vaccines will be safe for human administration and capable of
    generating measurable CD8 T cell responses to mutant tumor-specific antigens.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Personalized polyepitope DNA vaccine Experimental Participants will be treated by electroporation with 4 mg of a personalized polyepitope DNA vaccine at Day 1, Day 29 (+/1- 7 days), and Day 57 (+/- 7 days) with at least 21 days between injection days. Each DNA vaccination with be 4 mg vaccine administered intramuscularly using a TriGrid electroporation device.

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically confirmed diagnosis of invasive breast cancer.

    - ER and PR less than Allred score of 3 or less than 1% positive staining cells in the
    invasive component of the tumor

    - HER2 negative by FISH or IHC staining 0 or 1+.

    - Consented for genome sequencing and dbGAP-based data sharing and has provided or will
    provide germline and tumor DNA samples of adequate quality for sequencing.

    - Clinical stage T2-T4c, any N, M0 primary tumor by AJCC 7th edition clinical staging
    prior to neoadjuvant chemotherapy, with residual invasive breast cancer after
    neoadjuvant therapy. If the patient has invasive cancer or DCIS in the contralateral
    breast, she is not eligible for this study.

    - 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 2.5 X institutional upper limit of normal

    - AST/ALT 2.5 X institutional upper limit of normal

    - creatinine 1.5 X institutional upper limit of normal

    - Women of reproductive potential must agree to use adequate contraception (hormonal or
    barrier method of birth control; abstinence) prior to study entry and for the
    duration of study participation.

    - Able to understand and willing to sign an IRB-approved written informed consent
    document.

    Exclusion Criteria:

    - Evidence of progressive breast cancer within the last 30 days.

    - Received chemotherapy, radiotherapy, or biologic therapy within the last 30 days
    (neoadjuvant chemotherapy excluded).

    - Experiencing adverse events due to agents administered more than 30 days earlier.

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

    - Known metastatic disease.

    - Invasive cancer or DCIS in the contralateral breast.

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

    - Uncontrolled intercurrent illness including, but not limited to ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia (including sinus bradycardia), 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 pregnancy test is required no more than 7
    days before study entry.

    - The patient with a previous history of non-breast malignancy is eligible for this
    study only if the patient meets the following criteria for a cancer survivor. A
    cancer survivor is eligible provided the following criteria are met: (1) patient has
    undergone potentially curative therapy for all prior malignancies, (2) patients have
    been considered disease free for at least 1 year (with the exception of basal cell or
    squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).

    - Patient must have no active major medical or psychosocial problems that could be
    complicated by 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 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 of the personalized polyepitope DNA vaccine strategy, measured by both clinical observation and laboratory evaluation

    Secondary Outcome Measures

    Immunogenicity of the personalized polyepitope DNA vaccine strategy, measured by ELISPOT analysis, a surrogate for CD8 T cell function, and multiparametric flow cytometry

    Trial Keywords