Focused Ultrasound Therapy to Augment Antigen Presentation and Immune-Specificity of Checkpoint Inhibitor Therapy With Pembrolizumab in Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Change in Proportion of CD8+ Tumor Infiltrating Lymphocytes
研究概览
简要总结
This pilot study evaluates the use of high-intensity focused ultrasound (HIFU) combined with pembrolizumab in patients with metastatic breast cancer. One-half of participants will be randomized to receive the first dose of pembrolizumab after HIFU and one-half of participants will be randomized to receive their first dose of pembrolizumab before HIFU.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed metastatic or unresectable breast cancer
- •Any receptor status (estrogen receptor, progesterone receptor, HER2 receptor). Patients who are HR+ should also no longer be candidates for hormonal-based therapy. Patients who are HER2+ should have progressed on or no longer be candidates for available HER2 directed therapy. Hormonal therapy must be stopped prior to day 1 of treatment.
- •Patients must have had at least one prior line of therapy for breast cancer in the metastatic setting.
- •Patients must have an accessible lesion in the breast/chest wall/axilla which has not been previously thermally ablated. Prior breast irradiation is acceptable if the lesion has recurred or grown following radiation.
- •Patients must agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
- •Patients must have at least one target lesion in breast/chest wall/axilla which is amenable to application of high intensity focused ultrasound:
- •Patients must be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
- •Performance status of 0 or 1 on the ECOG Performance Scale.
- •Adequate organ function
排除标准
- •Patients currently participating and receiving study therapy or patients who have participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- •Patients with a diagnosis of immunodeficiency, patients receiving systemic steroid therapy or, patients who have received any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Patients with a known history of active Tuberculosis
- •Hypersensitivity to pembrolizumab or any of its excipients
- •Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day
- •Patients who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier are excluded.
- •Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day
- •Patients who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- •Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Active autoimmune disease that has required systemic treatment in the past 2 years.
- •History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- •Active infection requiring systemic therapy.
- •Pregnancy
- •Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent within the prior 24 weeks.
- •Known history of Human Immunodeficiency Virus (HIV)
- •Receipt of a live vaccine within 30 days of planned start of study therapy.
- •HIFU must not be applied to a breast with an implant. A region outside of the breast may be targeted as long as the targeted area is at least 10mm away from an implant.
研究组 & 干预措施
Arm A: 1st dose of pembrolizumab after HIFU
Pembrolizumab (200 mg) administered intravenously, days 22, 43, 64, followed by day 1 of each ensuing 3 -week cycle. Focused ultrasound tumor ablation day 15. High-intensity focused ultrasound ablation will target 50% of the tumor, up to 3 cubic centimeters.
干预措施: Pembrolizumab (Drug)
Arm A: 1st dose of pembrolizumab after HIFU
Pembrolizumab (200 mg) administered intravenously, days 22, 43, 64, followed by day 1 of each ensuing 3 -week cycle. Focused ultrasound tumor ablation day 15. High-intensity focused ultrasound ablation will target 50% of the tumor, up to 3 cubic centimeters.
干预措施: High-intensity focused ultrasound (HIFU) (Device)
Arm B: 1st dose of pembrolizumab before HIFU
Pembrolizumab (200 mg) intravenously, days 1, 22, 43, 64, followed by day 1 of each ensuing 3 -week cycle. Focused ultrasound tumor ablation day 15. High-intensity focused ultrasound ablation will target 50% of the tumor, up to 3 cubic centimeters.
干预措施: Pembrolizumab (Drug)
Arm B: 1st dose of pembrolizumab before HIFU
Pembrolizumab (200 mg) intravenously, days 1, 22, 43, 64, followed by day 1 of each ensuing 3 -week cycle. Focused ultrasound tumor ablation day 15. High-intensity focused ultrasound ablation will target 50% of the tumor, up to 3 cubic centimeters.
干预措施: High-intensity focused ultrasound (HIFU) (Device)
结局指标
主要结局
Change in Proportion of CD8+ Tumor Infiltrating Lymphocytes
时间窗: baseline and week 4
How many of the immune cells inside a tumor are a specific type of "killer" T cell
次要结局
未报告次要终点
研究者
Patrick Dillon, MD
Associate Professor
University of Virginia