Validation of the TheraSure CNI-Monitor Under Immuno-checkpoint-therapy (Hereinafter: "Immunotherapy") in NSCLC in Palliative Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 170
- 试验地点
- 3
- 主要终点
- PD
研究概览
简要总结
This is a prospective, non-interventional, national study planned at three centers for patients with non-curative NSCLC receiving immunotherapy.
At present, PD-L1 expression or tumor mutation burden serve as surrogate parameters for response to immunotherapy. However, the problem for clinicians is that not all patients with positive findings respond to this form of therapy.
Cell-free DNA (cf-DNA) can be detected in blood plasma. Tumor cells almost always have chromosomal instabilities (or "copy-number variations" (CNV)), which can be detected using next-generation sequencing (NGS), also in the cf-DNA. These CNV can be quantified and given as a cf-DNA copy number instability score (CNI value). TheraSure CNI-Monitor is a highly sensitive method that can detect as little as 0.5% tumor DNA in plasma.
In preliminary work in a cohort of 56 patients with various types of cancer (including: breast, colon, lung, ovary, melanoma) in advanced stages, the TheraSure CNI monitor was already evaluated in the monitoring of immunotherapy. In 51 of the 56 patients, increased CKD values were measured before the start of therapy compared to a normal group of 126 individuals. To predict the success of the therapy, further blood samples were used after the first and second therapy cycle and threshold values were set for the minimal expected decrease in the CNI value in the event of therapy response. A therapy failure could be predicted with a high positive predictive value, cases of hyperprogression could be detected earlier than by routine imaging. In addition, pseudoprogression could be distinguished from true progression using the CNI value.
The CNI monitor on cell-free DNA is to be used prospectively in 170 patients. The primary objective of the study is the prediction of primary progression under immunomonotherapy (defined as PD within 6 months after RECIST) with a predictive value for progression (PPV) of ≥50%.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
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
- •Signed informed consent form
- •Age ≥18 years
- •NSCLC, non-curatively treatable stage III or stage IV with palliative treatment indication
- •Immunocheckpoint-therapy for malignant disease (Immunotherapy as monotherapy, double immunotherapy or combination with chemotherapy)
排除标准
- •Person is unable to understand the nature, importance and scope of the clinical trial
- •Participation in an interventional study
- •Hb value <9g/dl
结局指标
主要结局
PD
时间窗: 6 months
The TheraSure CNI-Monitor predicts primary progression on immunomonotherapy (defined as PD within 6 months acc. to RECIST) with a predictive value for progression (PPV) of ≥50%.
次要结局
- PFS(6 months)
- OS(6 months)
研究者
Karsten Gavenis
on behalf of Principal Investigator Dr. Overbeck
University Medical Center Goettingen