The most important consideration in the design of this clinical trial is to ensure the safe
translation of the personalized synthetic long peptide vaccine strategy. The Food and Drug
Administration (FDA) dictates that initial studies of biologic therapies be performed in such
a way that there is a balance between the potential risks and benefits in individual
patients. Consistent with these recommendations, the investigators will target patients with
triple-negative breast cancer who do not have a pathologic complete response after
neoadjuvant chemotherapy. These patients typically have no gross evidence of disease
following standard of care therapy (neoadjuvant chemotherapy, surgery and radiation therapy)
but are at extremely high-risk for disease recurrence. Targeting this patient population
provides a window-of-opportunity to design and manufacture the personalized cancer vaccines,
maximizes the potential benefit from the vaccine as the regulatory networks associated with
metastatic disease are not present, and balances risk in this patient population with
extremely high risk for disease recurrence but no other treatment options.
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. Fresh
tissue is preferred (from biopsy at the time of port placement) but archival tissue is
allowed.
- 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 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/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
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 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.
