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.
- 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. Fresh
tissue is preferred (from biopsy at the time of port placement) but archival tissue is
- Clinical stage T1c-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 in the contralateral breast,
she is not eligible for this study.
- At least 18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status
- Adequate organ and marrow function no more than 14 days prior to registration as
- WBC ≥ 3,000/μL
- absolute neutrophil count ≥1,500/μL
- platelets ≥ 100,000/μL
- 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
- 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 any clinically significant adverse events above Grade 1 (according to
CTCAE 4.0) due to agents administered more than 30 days earlier. However, patients
with Grade 2 Alopecia will be considered eligible.
- Receiving any other investigational agent(s) or has received an investigational agent
within the last 30 days.
- Known metastatic disease.
- Invasive cancer 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, Sjogren'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