Local Therapy Optimization by Grouping Immune-modulation With Cryoablation (LOGIC) for High Risk Breast Cancers
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 36
- 主要终点
- Rate of Complete Pathological Response
研究概览
简要总结
Summary Points:
- High Risk Breast Cancers: Triple negative cancer is considered high risk due to high rate of local and systemic failure. Newer innovative treatment strategies are needed to improve systemic control of disease and survival.
- Immune system modulation: is an emerging modality in cancer treatment. Tumor antigens can stimulate T cells to identify and destroy cancer cells. Cancers express "altered self" antigens that tend to induce weaker responses than the "foreign" antigens expressed by infectious agents. Thus, immune stimulants and adjuvant approaches have been explored widely. Opportunities to develop effective cancer vaccines may benefit from seminal recent advances in understanding how immunosuppressive barricades are erected by tumors to mediate immune escape. This concept is precisely applicable to triple negative breast cancer due to their antigenicity. Checkpoint inhibitors are an attractive method for treatment of high-risk breast cancers. However, to leverage the efficacy of checkpoint inhibition, approaches are needed to enhance delivery of cancer antigens to the T cells.
- Cryoablation: offers an efficacious and safe method to enhance tumor antigen presentation to the immune cells while destroying the primary tumor. This ablation method is superior by virtue of antigen preservation in situ despite toxicity to the tumor cell. Impact of cryoablation in enhancing immunological responses in tumor microenvironment are well established; however, cryoablation can also cause tumor antigen tolerance via non-specific stimulation of T cells.
- Rationale for combining cryoablation and checkpoint inhibitors: Since checkpoint inhibitors curtail the tolerance developed by tumor antigens, and cryoablation enhances antigen presentation and T cell recruitment, it is intuitive that combination of these two approaches presents an ideal opportunity to leverage the benefits of both approaches while curtailing the limitations of either. Therefore, the investigators hypothesize in this study that their combination will improve the response rate and the degree of response.
详细描述
AIMS:
The main goal of proposed study is to assess synergy of tumor cryoablation and immune checkpoint inhibitor in high-risk breast cancer in humans. This will be achieved by comparing cryoablation alone and cryoablation in combination with pembrolizumab - a [checkpoint inhibitor (anti PD-1/PD-L1 antibody) currently FDA approved as cancer therapy] with the current standard of care including surgical resection. The current standard of neoadjuvant/ adjuvant therapies will remain unchanged for ethical reasons of providing best-known standard of care to all patients.
OBJECTIVES:
The investigators propose a prospective randomized exploratory trial where patients with clinical stage I/II, triple negative invasive breast cancer will be randomized to one of the three arms of the study:
- Standard of care - neoadjuvant therapy followed by surgical resection followed by appropriate adjuvant therapy as needed.
- Cryoablation arm - cryoablation followed by appropriate neoadjuvant therapy followed by surgical resection followed by appropriate adjuvant therapy as needed.
- Cryoablation with Pembrolizumab - Single dose of Pembrolizumab of 200 mg before (within 24-48 hours) of cryoablation followed by appropriate neoadjuvant therapy followed by surgical resection followed by appropriate adjuvant therapy as needed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Since proposed intervention ( cryoablation and immune therapy infusion) cannot be masked with placebo, only the data analyst will be masked.
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Stage I/II Cancer
- •Age range 18 - 90 years
- •Diagnoses: Invasive carcinoma, ER -, PR-, HER2- (triple negative)
- •Radiology findings: Unifocal disease visible on ultrasound
排除标准
- •Additional primary cancer
- •Inflammatory breast cancer
- •History of autoimmune disease
- •History of chronic immunosuppression
- •Prior immunotherapy
- •Recent vaccination (within 4 wks.)
- •Prior radiation therapy
- •Prior investigational agent therapy within last 1 year
- •Pregnancy at the time of diagnosis and/ or treatment
- •Breast feeding
研究组 & 干预措施
Standard of Care Arm:
Control arm: Stage I/II TNBC patients will receive neoadjuvant chemotherapy followed by lumpectomy/mastectomy with sentinel node biopsy +/- axillary dissection.
Intervention 1
Cryoablation Alone Arm: Intervention with cryoablation alone followed by neoadjuvant chemotherapy followed by lumpectomy/mastectomy with sentinel node biopsy +/- axillary dissection.
干预措施: Cryoablation (Device)
Intervention 2
Cryoablation + PD1 Inhibitor Arm: Intervention with cryoablation + Pembrolizumab followed by neoadjuvant chemotherapy followed by lumpectomy/mastectomy with sentinel node biopsy +/- axillary dissection.
干预措施: Cryoablation combined with PD1 Inhibitor (Combination Product)
结局指标
主要结局
Rate of Complete Pathological Response
时间窗: 6-8 months
Pathological analysis of tumor after completion of local and neoadjuvant therapy
次要结局
- Percent change is Tumor Infiltrating Lymphocytes Score(6-8 month)
- Percent change is Tumor Infiltrating Lymphocytes Score(6-8 month)
研究者
Rakhshanda Rahman
Professor Surgical Oncology
Texas Tech University Health Sciences Center