Prospective Evaluation of Immunological, Molecular-genetic, Image-based and Microbial Analyzes to Characterize Tumor Response and Control in Patients With Inoperable Stage III NSCLC Treated With Chemoradiotherapy Followed by Consolidation Therapy With Durvalumab (PRECISION)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Predictive biomarker for progression-free survival at 12 and 24 months
研究概览
简要总结
This non-interventional single-center explorative biomarker study aims at longitudinal comprehensive characterization (molecular genetics, immunological, morphological, image-based and microbial features) of the patient (host) and tumor as well as changes during standard treatment and in case of recurrent disease in inoperable stage III non-small cell lung cancer (NSCLC). Comprehensive analysis will include peripheral blood cellular and humoral immunophenotyping, circulating tumor DNA and gut/saliva microbiota analyses. 18F-FDG-PET/CT before, 6 weeks, 6- and 12-months after chemoradiotherapy as well as daily in course of radiation treatment cone-beam-CT and/or MRI imaging are included for morphological analysis. This study will provide valuable information of predictive biomarkers in patients with stage III NSCLC treated with durvalumab maintenance treatment after concurrent chemoradiotherapy.
详细描述
The study will enrol 40 patients with stage III inoperable non-small cell lung cancer (NSCLC) who received standard chemoradiotherapy followed by maintenance therapy with PD-L1 inhibition (durvalumab) according to the current European Medicines Agency (EMA) approval.
The oncological treatment is carried out according to the international standards of radiation oncology/medical oncology. These are implemented by the department of radiation oncology at the University Hospital Munich (LMU) in their SOPs. Therefore, all patients will be treated with concurrent platinum-based chemoradiotherapy followed by durvalumab maintenance treatment 12 months after the end of chemoradiotherapy at the department of radiation oncology (University Hospital Munich (LMU)). Comprehensive characterization of all patients includes immunophenotyping of peripheral blood mono-nuclear cells, ctDNA as well as gut/saliva microbiome analyses and will be performed before, after 15 fractions of radiotherapy, at the end of concurrent chemoradiotherapy as well as 3-, 6- and 12 months after start of durvalumab.
18F-FDG-PET/CT will be performed 5-10 d before start of radiotherapy, 6 weeks, 6 months,12 and 24 months after the end of chemoradiotherapy. Lung function will be assessed before start of radiotherapy, at the end and 6 weeks after chemoradiotherapy as well as 3-, 6- and 12, 18, 24 months after start of durvalumab.
Follow-up will be performed by the department of radiation oncology at the University Hospital Munich (LMU) according to the clinical SOPs.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 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
- •Patient age ≥ 18 years
- •Histologically/cytologically confirmed diagnosis of non-small-cell lung cancer (NSCLC)
- •Patients with non-operable NSCLC in tumor stage III A/B/C after UICC 8
- •Eligible for platinum-based concurrent chemoradiotherapy followed by durvalumab maintenance treatment
- •No invasive carcinoma in the last five years.
- •ECOG Performance Status 0-2
- •Lung function parameters (before or after bronchodilation): FEV1 ≥ 1.0 L and/or DLCO-SB ≥ 40%
- •A maximum of two cycles of induction chemotherapy are permissible before start of chemoradiotherapy
排除标准
- •Simultaneous participation in another clinical trial
- •Mixed histology of small-cell and non-small-cell lung cancer
- •Brain metastases confirmed by a contrast enhanced cMRI
- •Prior receipt of an immunotherapy or investigational medicinal product
- •Previous exposure to an anti-PD-1 or anti-PD-L1 antibody
- •Pneumonitis ≥ Grade 2 as a result of prior radio-/chemoradiotherapy
- •Patients with a non-active disease in the last 5 years can be included, but only after consultation with the responsible investigator of the study or his representative
- •Primary immunodeficiencies in previous history
- •Prior Interstitial lung disease (ILD)
- •Prior autoimmune disease
- •Previous organ transplantation with subsequent therapeutic immunosuppression
结局指标
主要结局
Predictive biomarker for progression-free survival at 12 and 24 months
时间窗: 24 months
To identify early immunological and morphological biomarkers and their dynamic changes to predict progression-free survival at 12 and 24 months.
次要结局
- Predictive biomarkers for progression-free survival, overall survival, response rate, local and distant tumor control(24 months)
研究者
Farkhad Manapov
PD Dr. med Farkhad Manapov
LMU Klinikum