A Pilot Study to Understand the Impact of Therapy With Tumour Treating Fields (TTFields) in NSCLC
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Molecular ctDNA characterization under concomitant TTFields therapy - cohort A (EGFR)
研究概览
简要总结
Low intensity, intermediate frequency (100-300 kHz) alternating electric fields, also known as Tumor Treating Fields (TTFields) were found to have a profound inhibitory effect on the growth rate of a variety of human cancer cells. Previous study showed anti-tumor activity in respect of melanoma, glioblastoma (GBM), breast carcinoma and NSCLC cell lines. This study aims to assess the impact of TTFields on NSCLC though the understanding of tumor evolution and peripheral lymphocytes activity and proliferation.
Concomitant to drug therapy, patients will receive treatment with Tumor Treating Fields (TTFields), generated by the medical device NovoTTF-200T with a recommended duration of minimum 18 h a day. TTFields administered using insulated transducer arrays applied to the skin surrounding the region of a malignant tumor.
50 patients will be recruited according to the study design in two cohorts and will receive TTFields therapy: Cohort A: Adult NSCLC EGFR positive mutation. Cohort B: Adult NSCLC patients to be treated with PD-1 inhibitors. The cohort A will focus on the clonal evolution in EGFR mutated lung cancer patients by using circulating tumor DNA (ctDNA) analysis of paired baseline and end-of-treatment (EOT) plasma samples. The cohort B will study the impact of TTField on the profile, activity, and proliferation of peripheral lymphocytes. Lymphocytes will be purified from whole blood samples for the profile, proliferation, and activity analyzed by FACS.
Treatment with TTFields will be administered until progressive disease, unacceptable toxicity1, withdrawal of consent or death. After the end of treatment, the patients will be followed until data cutoff date or 2 years after the last patient had entered the study.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients 18 years of age and older.
- •Have histologically or cytologically confirmed lung cancer.
- •Documented next generation sequencing assay performed on tumor sample in Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory.
- •Have at least 1 measurable lesion per RECIST v1.1
- •Have life expectancy ≥3 months.
- •Have Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Must provide a signed and dated informed consent indicating that the participants have been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.
- •Have the willingness and ability to comply with scheduled visits and study procedures.
- •Cohort A, confirmed EGFR mutation.
排除标准
- •Implanted electronic devices (e.g. pacemaker) in the upper torso.
- •Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ or prostate cancer, which are allowed within 3 years).
- •Have any condition or illness that, in the opinion of the investigator, would compromise participants' safety or interfere with the evaluation.
- •Be pregnant or breastfeeding.
结局指标
主要结局
Molecular ctDNA characterization under concomitant TTFields therapy - cohort A (EGFR)
时间窗: 5 years
The primary outcome measure will be the rate of new somatic mutation detection in circulating tumor DNA (ctDNA) using Next Generation Sequencing (NGS) in patients receiving concurrent TTFields therapy. The measure will be reported as the percentage of patients showing new somatic mutations upon progression of their disease following TTFields treatment.
Characterization of the impact of TTFields on peripheral lymphocytes proliferation ex-vivo - cohort B (PD-1 inhibitors treatment)
时间窗: 5 years
The primary outcome measure will be the quantification of peripheral lymphocyte proliferation in patients receiving PD-1 inhibitors therapy using an in vitro assay. Whole blood samples will be collected and the assay will involve the isolation, labeling, and analysis of peripheral lymphocytes with carboxyfluorescein diacetate succinimidyl ester (CFSE). Proliferation will be measured using flow cytometry (FACS) and the longitudinal changes in peripheral lymphocyte proliferation will be correlated with each patient's response to the therapy in cohort B.
In vitro peripheral lymphocytes activity characterization under concomitant TTFields therapy - cohort B (under PD-1 inhibitors treatment)
时间窗: 5 years
The primary outcome measure will be the evaluation of the impact of combining PD-1 inhibitors with TTFields therapy on peripheral lymphocyte activity using an in vitro assay. Whole blood samples will be collected and the assay will involve the isolation, activation, and labeling of peripheral lymphocytes from patients in cohort B with a panel of antibodies. The analysis will be performed using flow cytometry (FACS) and the longitudinal changes in peripheral lymphocyte activity will be correlated with each patient's response.
次要结局
- Objective response rate(5 years)
- DoR(5 years)
- Safety will be assessed by recording adverse events in both cohorts.(5 years)
研究者
Nir Peled
Head of Oncology
Shaare Zedek Medical Center