The Effect of Combined Cryotherapy and Immunotherapy on Systemic T Cell Changes and Clinical Outcomes in Metastatic Non-small Cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Changes in T Lymphocyte Count and Function in Response to Cryotherapy and Immunotherapy
研究概览
简要总结
Lung cancer remains one of the most commonly diagnosed oncological diseases worldwide and the first in terms of mortality. Although immune checkpoint inhibitors form the backbone of current metastatic non-small cell lung cancer treatments, there is still no ideal predictive marker for its efficacy and patients still achieve suboptimal results in overall response and survival. While immune checkpoint inhibitors are known to shift systemic anti-tumor immune response from suppression to stimulation in some patients, the investigators hypothesize that this effect can be further enhanced by cryotherapy, especially in "cold" tumors. If proven successful, cryotherapy in combination with immunotherapy, could potentiate a more powerful immune response compared to systemic therapy alone, improve overall response rate, patients' survival without disease progression, and overall survival. The investigators, therefore, aim to use combined local tumor cryotherapy, combined with immune checkpoint inhibitor therapy to induce and evaluate systemic anti-tumor T lymphocyte response and achieve improved non-small cell lung cancer patient outcomes than with immunotherapy alone.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with Eastern Cooperative Oncology Group (ECOG) performance score 0 - 1;
- •Patients with histologically confirmed metastatic non-small cell lung cancer and PD-L1 expression on tumor cells was evaluated;
- •CT examination shows measurable tumor formations according to the RECIST 1.1 criteria;
- •Primary lung tumor or metastasis accessible to flexible bronchoscopy;
- •Patients may have received surgery, adjuvant or neoadjuvant chemotherapy prior to the study if it was completed at least 12 months before relapse;
- •Patients informed about the purpose and course of the study and provided a written consent to participate.
排除标准
- •Patients who refused to participate in the clinical trial and did not sign the informed consent form;
- •Men and women under the age of 18, pregnant women;
- •Patients belonging to a vulnerable social group;
- •High risk of general anesthesia, defined as American Society of Anesthesiologists (ASA) class 4 - 6;
- •Documented allergy to medications used during general and local anesthesia, systemic cancer treatment;
- •Patients previously treated with immune checkpoint inhibitors;
- •EGFR mutations or ALK translocations have been identified in patients;
- •Patients with previously diagnosed autoimmune diseases, active viral hepatitis, uncontrolled human immunodeficiency virus (HIV) infection or untreated tuberculosis;
- •Patients treated with immunosuppressive drugs, systemic corticosteroids, with equivalent doses of prednisolone exceeding 10 mg/day;
- •Patients with an increased risk of bleeding during an interventional procedure;
- •Acute untreated conditions that would make it impossible to perform an interventional lung procedure.
研究组 & 干预措施
Cryotherapy and Pembrolizumab monotherapy;
Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab monotherapy (PD-L1 expression equal to or greater than 50%, no EGFR mutations or ALK translocations). Bronchoscopic cryotherapy procedure is performed before the start of systemic treatment.
干预措施: Bronchoscopic cryotherapy (Procedure)
Cryotherapy and Pembrolizumab monotherapy;
Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab monotherapy (PD-L1 expression equal to or greater than 50%, no EGFR mutations or ALK translocations). Bronchoscopic cryotherapy procedure is performed before the start of systemic treatment.
干预措施: Pembrolizumab (Drug)
Cryotherapy and Pembrolizumab with platinum-based chemotherapy;
Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab and platinum-based chemotherapy (PD-L1 expression less than 50%, no EGFR mutations or ALK translocations). Bronchoscopic cryotherapy procedure is performed before the start of systemic treatment.
干预措施: Bronchoscopic cryotherapy (Procedure)
Cryotherapy and Pembrolizumab with platinum-based chemotherapy;
Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab and platinum-based chemotherapy (PD-L1 expression less than 50%, no EGFR mutations or ALK translocations). Bronchoscopic cryotherapy procedure is performed before the start of systemic treatment.
干预措施: Pembrolizumab (Drug)
Cryotherapy and Pembrolizumab with platinum-based chemotherapy;
Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab and platinum-based chemotherapy (PD-L1 expression less than 50%, no EGFR mutations or ALK translocations). Bronchoscopic cryotherapy procedure is performed before the start of systemic treatment.
干预措施: Platinum based chemotherapy (Drug)
Pembrolizumab monotherapy;
Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab monotherapy (PD-L1 expression equal to or greater than 50%, no EGFR mutations or ALK translocations).
干预措施: Pembrolizumab (Drug)
Pembrolizumab with platinum-based chemotherapy;
Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab and platinum-based chemotherapy (PD-L1 expression less than 50%, no EGFR mutations or ALK translocations).
干预措施: Pembrolizumab (Drug)
Pembrolizumab with platinum-based chemotherapy;
Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab and platinum-based chemotherapy (PD-L1 expression less than 50%, no EGFR mutations or ALK translocations).
干预措施: Platinum based chemotherapy (Drug)
结局指标
主要结局
Changes in T Lymphocyte Count and Function in Response to Cryotherapy and Immunotherapy
时间窗: 6 weeks
Changes in T lymphocyte counts and function in peripheral venous blood assessed via flow cytometry
次要结局
- Objective response rate(1 year)
- Necrotic cancer cell death(6 weeks)
- The influence of immune cell infiltration in tumor tissue on subsequent cryotherapy and immunotherapy treatment(1 day)
- Progression-free survival(1 year)
- Overall survival(1 year)
- Changes in T Lymphocyte Effector Function in Response to Cryotherapy and Immunotherapy(6 weeks)
- Safety of bronchoscopic cryotherapy and immunotherapy(1 year)
- Changes in T Lymphocyte Function in Response to Cryotherapy and Immunotherapy(6 weeks)
研究者
Marius Zemaitis
Professor
Lithuanian University of Health Sciences