A Phase II Trial of The Immunogenicity of a DNA Plasmid Based Vaccine (STEMVAC) Encoding Th1 Selective Epitopes From Five Antigens Associated With Breast Cancer Stem Cells (MDM2, YB1, SOX2, CDC25B, CD105) in Participants With Early Stage Triple Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 33
- 试验地点
- 6
- 主要终点
- Cellular immune response: magnitude
研究概览
简要总结
This phase II trial studies the effect of DNA plasmid based vaccine (STEMVAC) in treating patients with patients with stage IB-III triple negative breast cancer. STEMVAC may wake up the immune system in patients who have had a diagnosis of triple negative breast cancer and have been treated. STEMVAC targets proteins that are expressed on breast cancer cells and works by boosting the immune system to recognize and destroy the invader cancer cell proteins that are causing the disease. The purpose of this trial is to test the immune system's response to STEMVAC.
详细描述
OUTLINE:
Patients receive STEMVAC vaccine with sargramostim intradermally (ID) every month for 3 months in the absence of disease progression or unacceptable toxicity. Patients then receive STEMVAC vaccine with sargramostim ID booster injections 3 months after the 3rd vaccination and 6 months after the 1st booster vaccination.
After completion of study treatment, patients are followed up at 28 days, and then annually for 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with triple negative breast cancer, stages IB, II or III. Estrogen receptor (ER)-negative and progesterone receptor (PR)-negative is defined as breast cancer with less than 10% of ER or PR expression. HER2 negative is defined as:
- •0-1+ HER2 expression by immunohistochemistry (IHC) OR
- •Fluorescence in situ hybridization (FISH) negative OR
- •HER2 2+ and FISH negative
- •Note: Participants with low ER positivity (≤10%) who are already on adjuvant hormonal therapy will be allowed on study and can continue their adjuvant hormonal treatment during study participation.
- •Participants must have completed all standard of care (or investigational) systemic therapy (including immune modulating agents) and radiotherapy if used between 28 and 365 days prior to enrollment
- •* Note: Treatment with a bisphosphonate or denosumab to prevent bone loss is not considered to be systemic therapy for breast cancer and its use within the 28 day pre-enrollment period or while on study is not exclusionary. Treatment with adjuvant olaparib within the 28 day pre-enrollment period or while on study is not exclusionary.
- •Participants must agree to avoid systemic steroids for the duration of the treatment period and until completion of the 1 month post 2nd booster vaccine visit (end of treatment)
- •Participants must be at least 18 years of age
- •* Note: Because no dosing or adverse event (AE) data are currently available on the use of STEMVAC in participants < 18 years of age, children and adolescents are excluded from this study but will be eligible for future pediatric trials, if applicable.
- •Participants must have Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1
- •White blood cell (WBC) >= 3000/mm^3 (within 60 days of enrollment and at least 28 days post standard of care [SOC] treatment)
- •Lymphocyte count >= 800/mm^3 (within 60 days of enrollment and at least 28 days post standard of care [SOC] treatment)
- •Platelet count >= 100,000/mm^3 (within 60 days of enrollment and at least 28 days post standard of care [SOC] treatment)
- •Hemoglobin (Hgb) >= 10 g/dl (within 60 days of enrollment and at least 28 days post standard of care [SOC] treatment)
- •Serum creatinine =< 1.2 mg/dl OR creatinine clearance > 60 ml/min (within 60 days of enrollment and at least 28 days post standard of care [SOC] treatment)
- •Total bilirubin =< 1.5 X upper limit of institutional normal (ULN) (within 60 days of enrollment and at least 28 days post standard of care [SOC] treatment)
- •AST (aspartate aminotransferase)/serum glutamic-oxaloacetic transaminase (SGOT) =< 1.5 X upper limit of institutional normal (ULN) (within 60 days of enrollment and at least 28 days post standard of care [SOC] treatment)
- •Must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses or condition precluding protocol treatment
- •The effects of STEMVAC on the developing human fetus are unknown. For this reason,
- •Female participant agrees to use adequate contraception (examples include: estrogen and/or progestogen containing hormonal contraception, barrier method (condom, cervical cap) or abstinence) while on the study and until 1 month after the 2nd booster vaccination when/if engaging in sex that could lead to pregnancy. Exceptions: Females who have had a hysterectomy, tubal ligation or bilateral oophorectomy OR meet one of the following criteria for postmenopausal: Age > 60 or age < 60 with >= 12 months amenorrhea and follicle-stimulating hormone (FSH) within the testing facility's postmenopausal range
- •Female participant agrees to inform her study physician immediately should she become pregnant or suspect she is pregnant while participating in this study
- •Male participants who are having sex that can lead to pregnancy must use an acceptable form of contraception (vasectomy with the absence of sperm, sexual abstinence, condoms) throughout the course of the study
- •Must be 14 days between a vaccine (i.e. COVID19, Flu, shingrix, Tdap, etc.) and any STEMVAC vaccination. **Note: This does not apply to the Td vaccine.
- •Patients must be willing to not undergo major elective surgical procedures with general anesthesia or conscious sedation through the end of treatment visit. (Note: port removal is allowable)
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Contraindication or known hypersensitivity to receiving sargramostim (rhuGM-CSF) or other products
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to STEMVAC
- •Participants receiving any other investigational agents
- •Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) is prohibited during the treatment period of the study, except when taken as low-dose (81 mg) aspirin therapy. Prohibited chronic use is defined as daily use for more than 7 days
- •Participants with any clinically significant autoimmune disease uncontrolled with treatment
- •Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant and breastfeeding women are excluded from this study
- •Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
- •* Note: These individuals are excluded in order to avoid confounding an existing condition with an immune response to STEMVAC
- •Chronic usage of immunosuppressants and glucocorticoids (methotrexate for RA, etc.)
- •History of invasive breast cancer prior to TNBC diagnosis * Note: Prior DCIS is allowable
研究组 & 干预措施
Prevention (STEMVAC vaccine, sargramostim)
Patients receive STEMVAC vaccine with sargramostim ID every month for 3 months in the absence of disease progression or unacceptable toxicity. Patients then receive STEMVAC vaccine with sargramostim ID booster injections 3 months after the 3rd vaccination and 6 months after the 1st booster vaccination.
干预措施: Sargramostim (Biological)
Prevention (STEMVAC vaccine, sargramostim)
Patients receive STEMVAC vaccine with sargramostim ID every month for 3 months in the absence of disease progression or unacceptable toxicity. Patients then receive STEMVAC vaccine with sargramostim ID booster injections 3 months after the 3rd vaccination and 6 months after the 1st booster vaccination.
干预措施: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine (Biological)
结局指标
主要结局
Cellular immune response: magnitude
时间窗: At 10 months after 3rd vaccination
Defined by the magnitude of development of the Th1 (IFN-gamma \[g\]) antigen specific immune response against STEMVAC antigens using enzyme-linked immunosorbent spot assay (ELISPOT). The magnitude of immune response is defined as the sum of the corrected spots/well values calculated at each time point.
Cellular immune response: incidence
时间窗: At 10 months after 3rd vaccination
Defined by the incidence of development of the Th1 (IFN-gamma \[g\]) antigen specific immune response against STEMVAC antigens using enzyme-linked immunosorbent spot assay (ELISPOT).
次要结局
- Incidence of adverse events(1 month after last booster vaccine)
- Kinetics of the magnitude of antigen specific IFN-gamma ELISPOT counts(13 months)
- Activation status and repertoire diversity of peripheral blood T-cells(Prior to and after STEMVAC vaccination)
- Relapse free survival (RFS)(Up to 5 years)