Neoadjuvant Multi-epitope HER2 Peptide Vaccine in Patients With HER2-expressing DCIS

This is an interventional clinical study examining the safety and efficacy of a degenerate
subdominant HER2 specific helper T cell epitope vaccine (H2NVAC) in patients with
HER2-expressing ductal carcinoma in situ (DCIS). The ultimate goal of this vaccine is to
prevent future invasive breast cancer among patients who are diagnosed with DCIS. However,
the focus of this study is safety and efficacy. The vaccine consists of 4 peptide epitopes
(15-18 amino acids in length) derived from the HER2 protein. These peptides are derived from
HER2 and were selected based upon their recognition by lymphocytes from women with prior
HER-2 positive breast cancer. To enhance immunity, the peptides are admixed with the adjuvant
GM-CSF. Patients will receive four bi-monthly vaccinations followed by surgery as diagrammed
below; observation includes periodic blood draws to assess toxicity and immune responses, as
well as periodic echocardiography to assess left ventricular ejection fraction.

Eligibility

Criteria:

Inclusion Criteria

- Female age ≥ 18 years.

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

- Patients must not have received any prior therapy for current DCIS.

- Note: Patients who received tamoxifen or raloxifene or another agent for prevention of
breast cancer may be included as long as the patient has discontinued the treatment at
least 2 months prior to baseline study biopsy.

- Note: Concurrent use of endocrine therapy during the vaccination/preoperative period
is not allowed. However, standard adjuvant endocrine therapy with tamoxifen or
aromatase inhibitor after completion of vaccination and surgery is allowed.

- Patients must be agreeable to have an additional research biopsy prior to the first
vaccination.

- Patients must have evidence of at least 1.0 cm of disease extent based on mammogram or
ultrasound imaging.

- Patients must have adequate organ and marrow function less than or equal to 28 days
prior to Pre-Registrationas defined below:

- Absolute neutrophil count (ANC) ≥ 1500/mm3

- Platelet count ≥ 75,000/mm3

- Hemoglobin ≥ 9.0 g/dL

- Creatinine ≤2 x ULN

- SGOT (AST) ≤ 2 x ULN

- Albumin ≥ 3 g/dL

- Negative serum pregnancy test done ≤ 7 days prior to Pre-registration, for women of
childbearing potential only.

- Willing to employ adequate contraception from the time of Pre-registration through 6
months after the final vaccine cycle.

- Note: Adequate contraception methods include birth control pills, barrier device,
intrauterine device.

- Capable of understanding the investigative nature, potential risks, and benefits of
the study.

- Capable of providing valid informed consent.

- Willing to return to enrolling institution for all study visits (immunizations, blood
draws, etc).

- Willing to provide blood samples for correlative research purposes

- Willing to receive a tetanus vaccination if subject has not had one within the past
year.

Exclusion Criteria

- Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown:

- Pregnant women

- Nursing women unwilling to stop breast feeding

- Women of child bearing potential who are unwilling to employ adequate contraception
from the time of registration through 6 months after the final vaccine cycle.

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens.

- Immunocompromised patients including patients known to be HIV positive or those on
chronic steroids.

- Note: Must be off systemic steroids greater than or equal to 90 days prior to
Pre-registration. However, topical steroids, inhalants or steroid eye drops are
permitted.

- 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.

- Uncontrolled acute or chronic medical conditions including, but not limited to the
following:

- Active infection requiring antibiotics

- Congestive heart failure with New York Heart Association class III or IV; moderate to
severe objective evidence of cardiovascular disease

- Myocardial infarction or stroke less than or equal to 6 months prior to
Pre-Registration

- Receiving any other investigational agent.

- Other active malignancy at time of Pre-registration or less than or equal to the last
three years prior to Pre-registration. EXCEPTIONS: Non-melanoma skin cancer or
carcinoma-in-situ (e.g. of cervix, prostate). NOTE: If there is a history of prior
malignancy, they must not be receiving other specific treatment (cytotoxics,
monoclonal antibodies, small molecule inhibitors) for their cancer.

- Known history of autoimmune disease, including Type I diabetes.

- Any prior hypersensitivity or adverse reaction to GM-CSF.

- History of trastuzumab-related cardiac toxicity requiring interruption or
discontinuation of therapy, even if LVEF fully recovered.

- Baseline LVEF with a value below 55%.

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment.

- History of myocardial infarction ≤ 168 days (6 months) prior to Pre-registration, or
congestive heart failure requiring use of ongoing maintenance therapy for life
threatening ventricular arrhythmias.