Immunotherapy Clearance and Phenotype of Circulating Tumor Cells in Patients With Lung and Head and Neck Cancers, Treated With an Immunotherapy-based Therapy
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 75
- 试验地点
- 4
- 主要终点
- Immunotherapy clearance (mL/min) and number of PD-L1 (absolute number) positive CTCs after two cycles of treatment (composite criteria)
研究概览
简要总结
Immunotherapy is widely administrated as anticancer treatment in metastatic setting. Despite a proved efficacy in several cancer types and clinical situations, it exists a wide variability of responses in terms of efficacy and toxicity. The rate of responders depends mostly on the type of pathology, with 40% of responders among melanoma patients, 20-30% among lung and head and neck cancer patients and only 1% of responders among pancreatic cancer patients. Thus, the main challenge today is to be able to select patients for whom the treatment is likely to be effective. Several studies suggested that tumors with a high mutational burden and expressing PD-L1 are better responders to immunotherapy.
However, a proportion of PD-L1 negative cancers responds to immunotherapy, suggesting that other parameters have to be considered together with PD-L1 expression. Of that, the immunotherapy clearance seems to have an impact on overall survival, but larger studies, including different molecules and cancer types, are needed to better understand the correlation between the clearance and the response to immunotherapy.
Tumor cells released from the primary tumor in the blood circulation (CTCs, for circulating tumor cells) are considered as "liquid biopsies", as they contain the entire genetic and phenotypic information representative of the tumor, including PD-L1 expression. Thus, the variation of PD-L1 expression under treatment can be easily followed-up on blood samples collected during the time.
The objective of MADMAS is to study the correlation between the immunotherapy clearance, measured at the different times during treatment, and the variation of the number of CTCs expressing PD-L1 after two cures of treatment.
MADMAS will enroll patients with lung or head and neck cancers, treated with an immunotherapy-based therapy. Blood samples will be collected at the baseline and before the first two cures of treatment. The immunotherapy clearance will be measured with an innovative approach of Mass Spectrometry, and PD-L1 expression will be measured on CTCs, purified with a highly sensitive microfluidics technology.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Lung cancer (n= 30):
- •Adult patients
- •Patients who gave its written informed consent to participate to the study
- •Weight at inclusion ≥ 48 kg
- •NSCLC histology only
- •Stage IV according to 8th TNM classification
- •Planned to be treated with immunotherapy (+/- chemotherapy) as a first line treatment in metastatic setting
- •PD-L1 status on primary tumor available at the inclusion
- •Patients affiliated to a social insurance regime
- •Head and neck cancer (n= 30):
- •Adult patients
- •Patients who gave its written informed consent to participate to the study
- •Weight at inclusion ≥ 48 kg
- •Recurrent or metastatic epidermoid carcinomas from oral cavity, oropharynx, hypopharynx, larynx (except nasopharynx)
- •Stage IV according to 8th TNM classification
- •Planned to be treated with immunotherapy (+/- chemotherapy)
- •PD-L1 status on primary tumor available at the inclusion
- •Patients affiliated to a social insurance regime
排除标准
- •History of previous cancers, except for adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, treated and with no evidence of disease for ≥ 5 years
- •Patients under tutorship or guardianship
- •Pregnant or breast feeding women
- •Patients under psychiatric care
- •Exclusion Criteria specific pour head and neck cohort:
- •- Patients already treated with immunotherapy
研究组 & 干预措施
cancer patients
MADMAS will include 30 patients with metastatic NSCLC and 30 patients with metastatic head and neck cancers; patients will NSCLC will receive an immunotherapy-based treatment in first line metastatic setting; patients with head and neck cancers are included if they are planned to receive an immunotherapy-based treatment, whatever the line.
干预措施: Blood draws (Other)
结局指标
主要结局
Immunotherapy clearance (mL/min) and number of PD-L1 (absolute number) positive CTCs after two cycles of treatment (composite criteria)
时间窗: At the end of cycle 2 (each cycle is 21 days)
The clearance and the number of PD-L1 positive cells will be measured on blood samples collected the day of the third immunotherapy administration (each cycle is 14 to 28 days, depending on the type of immunotherapy).
次要结局
- Baseline transcriptomic profile of CTCs isolated form peripheral blood(Day 1 of cycle 1, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment))
- identification of CTCs transcriptomic signatures, associated to immunotherapy efficacy or toxicity(2 years)
- Progression free survival(2 years)
- Overall survival(2 years)
- level of PD-L1 expression on primary tumor tissue(2 years)
- 1st cycle transcriptomic profile of CTCs isolated form peripheral blood(Day 1 of cycle 2, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment))
- 2nd cycle transcriptomic profile of CTCs isolated form peripheral blood(Day 1 of cycle 3, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment))