I. Evaluate for nelipepimut-S-specific cytotoxic T lymphocyte (CTL; cluster of differentiation [CD]8+ T cell) response in vaccinated patients compared to patients receiving GM-CSF (sargramostim) alone.
I. Toxicity profile and frequency of adverse events in women with ductal carcinoma in situ (DCIS) of the breast receiving nelipepimut-S vaccine (nelipepimut-S plus GM-CSF vaccine) as compared to women receiving GM-CSF alone.
II. In vivo immune response to nelipepimut-S determined by delayed type hypersensitivity reaction; III. Immune response to other tumor antigens (epitope spreading). IV. Functional capacity of the immune response to vaccination. V. Determine CTL functional capability using intracellular cytokine assays. VI. Evaluate polyfunctional cytokine responses assessed by multiplex assay. VII. Presence of DCIS at resection. VIII. Difference in human epidermal growth factor receptor 2 (HER2) expression in the biopsy and the surgical specimen excised post-vaccination.
IX. Histologic responses: degree of lymphocyte infiltration determined on hematoxylin and eosin (H&E) stained slides and by immunohistochemistry staining for CD3, CD4 and CD8.
X. Histologic responses: proliferation-related Ki-67 antigen (Ki67) in DCIS cells (proliferation).
XI. Histologic responses: cleaved caspase 3 in DCIS cells (apoptosis). XII. Immune infiltrates in normal tissue maximally distant from the tumor (in mastectomy samples).
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive nelipepimut-S plus GM-CSF vaccine intradermally (ID) 3 vaccination 2 weeks apart prior to surgery.
ARM II: Patients receive sargramostim ID 3 vaccinations 2 weeks apart prior to surgery, and 3 vaccinations 1 months apart post-surgery.
After completion of study treatment, patients are followed up at 1 and 3 months.
- Participants must have a diagnosis of DCIS made by core needle biopsy
- Participants must have an area of radiographic abnormality measuring at least 1 cm
- Participants must be human leukocyte antigen (HLA)-A2 positive
- Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 (Karnofsky >= 60%)
- Absolute neutrophil count >= 1,500/mm^3
- Platelets >= 100,000/mm^3
- Hemoglobin >= 10 g/dL
- Blood urea nitrogen =< 2 x upper limit of normal (ULN)
- Alkaline phosphatase =< 2 x ULN
- Lactate dehydrogenase =< 2 x ULN
- Creatinine =< 2 x ULN
- Bilirubin =< 2 x ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x ULN
- Willingness to comply with all study interventions and follow-up procedures
- A normal ejection fraction, as defined by the participant's institution; only limited echocardiograms (echos) will be used as cardiac evaluation; no other tests are allowed; ECHO is to be done only in HLA-A2 positive participants
- The ability to understand and willingness to sign a written informed consent document
- Bilateral breast malignancy or an unconfirmed, nonmalignant but suspicious mass in the opposite breast to include atypical ductal hyperplasia
- Invasive breast cancer
- History of prior breast cancer
- History of prior ductal carcinoma in situ (DCIS); prior lobular carcinoma in situ (LCIS) is allowed
- Pregnant, unwilling to use adequate contraception during study treatment duration or breastfeeding; pregnant women will be excluded; women of child-bearing 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 OR be post-menopausal defined as any one of the following 1) prior hysterectomy, 2) absence of menstrual period for 1 year in the absence of prior chemotherapy or 3) absence of menstrual period for 2 years in women with a prior history of chemotherapy exposure who were pre-menopausal prior to chemotherapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
- Any autoimmune disease or other medical condition that, in the opinion of the investigator, would compromise the subject's safety
- Immune deficiency diseases such as immunoglobulin deficiency or immunosuppressive therapy that might interfere with appropriate immune response
- Known history of or known active infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C
- Patients on chronic steroid therapy or other immunosuppressive therapy except for topical steroids
- Patients with a known hypersensitivity to GM-CSF, yeast-derived products, or any component of the GM-CSF product (e.g., mannitol)
- Concurrent treatment with other investigational agent
- History of non-breast malignancy within 5 years prior to randomization, except curatively treated superficial bladder cancer, carcinoma in situ of the cervix (stage 0-1), and basal cell or squamous cell carcinoma of the skin
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to NeuVax
- 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 situations that would limit compliance with study requirements
- No recent or planned immunotherapy
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||18 Years|