Clinical trial NCT05198154: ctDNA Analysis to Monitor the Risk of Progression After First-line Immunotherapy in Patients With Advanced NSCLC
Official title: A Multicenter, Prospective Clinical Study of Circulating Tumor DNA Analysis to Monitor the Risk of Progression After Long-term Benefit to First-line Immunotherapy in Patients With Advanced NSCLC (CR1STAL)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Advanced Lung Non-Small Cell Carcinoma
Keywords: ctDNA
advanced lung cancer
first-line immunotherapy
the risk of progression
minimal residual disease (MRD)
long-term benefit
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: Sun Yat-sen University
name: First Affiliated Hospital Xi'an Jiaotong University
name: Fujian Cancer Hospital
name: Third Affiliated Hospital of Third Military Medical University
name: Xiangya Hospital of Central South University
name: Qinghai Province Tumor Hospital
name: Wuhan Union Hospital, China
name: Zhejiang Provincial People's Hospital
name: Hunan Province Tumor Hospital
name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Zhejiang Cancer Hospital
name: The First Affiliated Hospital of Guangzhou Medical University
name: Inner Mongolia People's Hospital
name: Guizhou Provincial People's Hospital
name: The Third Xiangya Hospital of Central South University
name: Yueyang Central Hospital
name: ZhuZhou Central Hospital
name: Zhangjiajie Affiliated Hospital of Hunan Normal University
name: Loudi Central Hospital
name: Chang Sha First Hospital
First posted: 2022-01-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Clinically confirmed advanced NSCLC patients with long-term benefit after first-line immunotherapy

Brief summary: This study aims to explore the correlation of circulating tumor DNA(ctDNA) and the risk of progression in patients with advanced NSCLC who have long-term benefit from first-line immunotherapy (PFS 12 months)

Detailed description: Evidence suggests that circulating tumor DNA (ctDNA) analysis can noninvasively identify minimal residual disease (MRD) in clinical oncology. The researches will be sharply increased about ctDNA potential clinical application in the near future. In the early stage of NSCLC, ctDNA has been indicated to identify those at high risk of recurrence after radical surgery. And this study will focus on those patients with advanced NSCLC who have long-term benefit from first-line immunotherapy (PFS 12 months). 10ml plasma will be collected every three months until disease progression to interrogate ctDNA by high-depth panel sequencing, exploring its prediction value about the risk of progression. Meanwhile, the investigators would like to explore the lead time of detectable ctDNA before regular imaging finding.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Advanced non-small cell lung cancer (stage IIIB-IV), pathological types limited to squamous cell carcinoma or non-squamous cell carcinoma, driver gene mutations (EGFR/ALK/ROS1) were negative
* General condition: ECOG score 0 or 1
* First-line monotherapy or combination immunotherapy
* The long-term benefit of immunotherapy was defined as PFS=12months
* Tumor tissue samples can be obtained at the time of enrollment, and at least 5 \~ 10 sections can be generated, and the pathological report indicates that the overall tumor content is not less than 10% or NGS testing with a fixed-panel is available; or no tumor tissue is available.
* At least one measurable lesion (except patients with CR after first-line treatment) can be evaluated according to RECIST1.1 standard.
* Have self-awareness, be able to understand the research scheme and voluntarily participate in the study, and can sign the informed consent form
* Have good compliance, be able to cooperate with the collection of specimens from each node and provide corresponding clinical information.

Exclusion Criteria:

* Serious primary diseases of the heart, liver and kidney
* Other malignant tumors within 3 years prior to diagnosis of NSCLC
* Women in pregnancy and lactation
* The active stage of human immunodeficiency virus (HIV) infection
* Patients with active systemic infection, pneumonia, tuberculosis, pericarditis
* Patients who cannot understand the content of the experiment and cannot cooperate and refuse to sign informed consent.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 3 years
Secondary outcomes:
measure: The correlation of ctDNA and risk of progression
timeFrame: 3 years
measure: Lead time
timeFrame: 3 years
measure: Incidence of adverse events
timeFrame: 3 years
measure: Overall survival (OS)
timeFrame: 3 years
Other outcomes:
measure: Objective response rate (ORR)
timeFrame: 3 years
measure: Factors influencing ctDNA detection
timeFrame: 3 years
measure: Differences between ctDNA MRD and other peripheral blood biomarkers.
timeFrame: 3 years
Locations:
city: Changsha
country: China
facility: Oncology Department，Second Xiangya Hospital of Central South University
state: Hunan
Study officials:
References: