This phase Ib trial studies the side effects and best dose of a vaccine called H2NVAC before surgery in treating patients with HER2 expressing ductal carcinoma in situ. H2NVAC is a vaccine designed to stimulate specialized white blood cells in hopes of increasing immune response and protecting against breast cancer.
Recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| Granulocyte-Macrophage Colony-Stimulating Factor | Colony Stimulating Factor 2, Colony Stimulating Factor, Granulocyte-Macrophage, Colony-Stimulating Factor, Colony-Stimulating Factor 2, CSF, CSF2, GM CSF, GM-CSF, GMCSF, Granulocyte Macrophage Colony Stimulating Factor, Granulocyte Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony Stimulating Factor | Treatment (multi-epitope HER2 peptide vaccine H2NVAC, GM-CSF) |
| Multi-epitope HER2 Peptide Vaccine H2NVAC | H2NVAC, HER2 Peptide Vaccine H2NVAC, HER2 Specific Helper T-cell Epitope Vaccine H2NVAC | Treatment (multi-epitope HER2 peptide vaccine H2NVAC, GM-CSF) |
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of multi-epitope HER2 peptide vaccine H2NVAC
(H2NVAC) given every 2 weeks for 4 cycles in patients with HER2 expressing ductal carcinoma
in situ (DCIS) prior to surgery.
II. To determine the dose level of H2NVAC with maximum systemic and intratumoral
immunogenicity as measured by activated HER2-specific T lymphocytes or high-affinity
antibodies.
SECONDARY OBJECTIVES:
I. To determine intratumoral immunogenicity of H2NVAC in patients with HER2-expressing DCIS.
II. To assess the complete pathological response after 4 cycles of neoadjuvant H2NVAC.
III. To assess the systemic immunogenicity of H2NVAC in patients with HER2-expressing DCIS.
IV. To assess changes in HER2 expression in the DCIS after 4 cycles of neoadjuvant H2NVAC.
V. To assess the distribution of the helper T cell response among T helper cell
differentiation states.
OUTLINE: This is a dose-escalation study of multi-epitope HER2 peptide vaccine H2NVAC.
Prior to standard of care surgery, patients receive granulocyte macrophage-colony-stimulating
factor (GM-CSF) admixed with multi-epitope HER2 peptide vaccine H2NVAC intradermally on day
1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression
or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, and 12 months after
surgery and optionally at 18 and 24 months after surgery.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Treatment (multi-epitope HER2 peptide vaccine H2NVAC, GM-CSF) | Experimental | Prior to standard of care surgery, patients receive GM-CSF admixed with multi-epitope HER2 peptide vaccine H2NVAC intradermally on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. |
|
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients must not have received any prior therapy for current DCIS
- Note: Patients who received tamoxifen, raloxifene, aromatase inhibitor 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 if
they chose to have this collected
- 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
- Any degree of HER2 expression as performed on the diagnostic clinical biopsy defined
by immunohistochemistry +1, +2, or +3
- Histologically confirmed un-resected operable ductal carcinoma in situ with no
evidence of lymph node involvement or distant metastasis
- Patients will be asked to have an additional research biopsy prior to the first
vaccination. This is not mandatory for participation
- Patients must have evidence of at least 1.0 cm of disease extent based on mammogram or
ultrasound imaging
- Absolute neutrophil count (ANC) >= 1500/mm^3 (less than or equal to 28 days prior to
registration)
- Platelet count >= 75,000/mm^3 (less than or equal to 28 days prior to registration)
- Hemoglobin >= 9.0 g/dL (less than or equal to 28 days prior to registration)
- Creatinine =< 2 x upper limit of normal (ULN) (less than or equal to 28 days prior to
registration)
- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2
x ULN (less than or equal to 28 days prior to registration)
- Albumin >= 3 g/dL (less than or equal to 28 days prior to registration)
- Negative serum pregnancy test done =< 7 days prior to Registration, for women of
childbearing potential only
- Willing to employ adequate contraception from the time of 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 human immunodeficiency virus
(HIV) positive or those on chronic steroids
- Note: Must be off systemic steroids greater than or equal to 90 days prior to
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
registration
- Receiving any other investigational agent
- Other active malignancy at time of registration or less than or equal to the last
three years prior to 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 left ventricular ejection fraction (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 registration, or
congestive heart failure requiring use of ongoing maintenance therapy for life
threatening ventricular arrhythmias
- History of ipsilateral radiation to the current affected breast with DCIS
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
| Measure: | Adverse events |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | Number of adverse events reported. |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Mayo Clinic |
September 4, 2020
