Phase Ib Study of Neoadjuvant DPX-Survivac, Aromatase Inhibition, and With/Without Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Number of participants without the following safety events: TASAEs, persistent grade III/IV TAAEs, or toxicity-related delays in curative-intent surgery. Toxicity graded by CTCAE v5.0 and monitoring of AEs performed per FDA and NCI guidelines.
研究概览
简要总结
The study seeks to establish the safety of neoadjuvant aromatase inhibitor with: DPX-Survivac, DPX-Survivac plus radiation, or DPX-Survivac with cyclophosphamide in stage I to III HR+HER2- breast cancer. There will be sequential enrollment into 3 arms with an anticipated N=6 participants per arm for N=18 participants in total. All participants will receive letrozole 2.5 mg daily during the 6 weeks of neoadjuvant therapy. Neoadjuvant therapy occurs weeks 1-6, with standard of care surgery taking place week 7 to 9.
详细描述
Women with hormone receptor positive, HER2-negative (HR+/HER2-) breast cancer with large tumors or positive lymph nodes have low response rates with neoadjuvant chemotherapy. Survivin is overexpressed in HR+HER2- breast cancer. Increasing tumor-specific Th1 immunity by administration of DPX-Survivac may alter the immune environment of these tumors. Radiation is a standard component of breast cancer therapy causing a reduction in local recurrences and improved breast cancer specific survival. Low dose cyclophosphamide can deplete regulatory T-cells without altering levels of effector T-cells. The investigators predict that combining a vaccine targeting Survivin, overexpressed in HR+HER2- tumors, with other immune modulating therapies such as radiation or low dose cyclophosphamide can enhance the efficacy of DPX-Survivac.
Primary Objective
1) Safety of neoadjuvant aromatase inhibitor with: DPX-Survivac, DPX-Survivac plus radiation, or DPX-Survivac with cyclophosphamide in stage I to III HR+HER2- breast cancer Secondary Objectives
- Immunogenicity of each arm, assessed by IFN-γ ELISPOT in PBMC.
- Immunogenicity of each arm, assessed by GEO-Mx digital spatial profiler evaluation of FFPE tissue and TCRβ evaluation for surviving-specific T cells in the tumor.
Exploratory Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients must provide informed consent prior to any study-specific procedures and be able to understand and be willing to sign an informed consent document. Results of standard-of-care tests or examinations performed prior to obtaining informed consent and prior to treatment may be used for screening assessments rather than repeating such evaluations if within 30 day of day
- •Women with resectable, non-metastatic breast cancer that is >1 cm, hormone receptor positive, HER2 negative, Ki67>10%.
- •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
- •Patients must be at least 28 days post systemic steroids prior to enrollment.
- •Patients must be at least 18 years of age.
- •Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status Score of ≤ 1
- •Adequate laboratory values within 30 days of enrollment defined as follows:
- •White blood cell (WBC) ≥ 3000/mm3
- •Hemoglobin (Hgb) ≥ 9 g/dL
- •Neutrophil count ≥ 1500/mm3
- •Lymphocyte count ≥ 1000/mm3
- •Platelet count ≥ 75,000/mm3
- •Serum creatinine ≤ 2.0 mg/dL or creatinine clearance > 60 ml/min
- •Total bilirubin ≤ 1.5 mg/dL
- •Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) ≤ 2 times the ULN-
- •Patients must have recovered from major infections and, in the opinion of the investigator, do not have any significant active concurrent medical illnesses precluding protocol treatment.
- •The effects of DPX-Survivac on the developing human fetus are unknown. Women on the trial should be post-menopausal based on the NCCN definition of menopause
- •For patients in Arm B only, they must be able to undergo MR imaging as determined by treating physician using the standard Radiation Oncology MR screening process
排除标准
- •Patients may not be receiving any other investigational agents or on concurrent clinical trials while on during the clinical trial period.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to DPX-Survivac.
- •Pregnant and pre-menopausal women are excluded from this study because to keep anti-endocrine therapy consistent between patients.
- •Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C.
- •Uncontrolled autoimmune disease. Autoimmune disease allowed if controlled (with or without treatment) for the last 12 months.
- •Patients may not have received or plan to receive neoadjuvant systemic chemotherapy. 7) Patients unable to receive an aromatase inhibitor
- •8) Prior radiation to the affected breast 9) Previous cancers except for non-melanoma skin cancers or high risk cervical lesions in the past 5 years.
- •10) Previous breast cancer, tamoxifen, or aromatase inhibitor use. 11) Previous investigational immune therapy use-
研究组 & 干预措施
Arm A: DPX-Survivac, Letrozole
Letrozole 2.5 mg po daily, DPX-Survivac 0.25 mL SC week 2 and Week 5
干预措施: Letrozole 2.5mg (Drug)
Arm B: DPX-Survivac, Letrozole, Radiation
Letrozole 2.5 mg po daily, XRT 10 Gy x 2, DPX-Survivac 0.25 mL SC week 2 and Week 5
干预措施: Letrozole 2.5mg (Drug)
Arm B: DPX-Survivac, Letrozole, Radiation
Letrozole 2.5 mg po daily, XRT 10 Gy x 2, DPX-Survivac 0.25 mL SC week 2 and Week 5
干预措施: XRT 10Gy x2 (Radiation)
Arm B: DPX-Survivac, Letrozole, Radiation
Letrozole 2.5 mg po daily, XRT 10 Gy x 2, DPX-Survivac 0.25 mL SC week 2 and Week 5
干预措施: DPX-Survivac (Biological)
Arm A: DPX-Survivac, Letrozole
Letrozole 2.5 mg po daily, DPX-Survivac 0.25 mL SC week 2 and Week 5
干预措施: DPX-Survivac (Biological)
Arm C: DPX-Survivac, Letrozole, cyclophosphamide
Letrozole 2.5 mg po daily, cyclophosphamide 50 mg po BID, DPX-Survivac 0.25 mL SC week 2 and Week 5
干预措施: DPX-Survivac (Biological)
Arm C: DPX-Survivac, Letrozole, cyclophosphamide
Letrozole 2.5 mg po daily, cyclophosphamide 50 mg po BID, DPX-Survivac 0.25 mL SC week 2 and Week 5
干预措施: Cyclophosphamide 50mg (Drug)
Arm C: DPX-Survivac, Letrozole, cyclophosphamide
Letrozole 2.5 mg po daily, cyclophosphamide 50 mg po BID, DPX-Survivac 0.25 mL SC week 2 and Week 5
干预措施: Letrozole 2.5mg (Drug)
结局指标
主要结局
Number of participants without the following safety events: TASAEs, persistent grade III/IV TAAEs, or toxicity-related delays in curative-intent surgery. Toxicity graded by CTCAE v5.0 and monitoring of AEs performed per FDA and NCI guidelines.
时间窗: The safety assessment period begins with day 1 and ends within 30 days of surgical excision.
yes/no outcome variable, ascertained for each individual subject, and reported as a binomial proportion for each arm. Safety will be reported for all subjects who receive at least one dose of drug/radiation/study therapy
次要结局
- Immunogenicity of each therapeutic arm IFN-γ ELISPOT(throughout the study day 1, Day 8, Day 15, Day 29, Day 36, Week 7-9, Week 11, and 6 months post-surgery)
- Immunogenicity of each therapeutic arm GEO-Mx digital spatial profiler(throughout the study day 1, Day 8, Day 15, Day 29, Day 36, Week 7-9, Week 11, and 6 months post-surgery)