ctDNA Analysis to Monitor the Risk of Progression After First-line Immunotherapy in Patients With Advanced NSCLC (CR1STAL)

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)

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)

Study Overview

• Status: Recruiting
• Conditions: Advanced Lung Non-Small Cell Carcinoma
• Intervention / Treatment: Diagnostic test: ctDNA detection

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.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Chunhong Hu, professor; Phone Number: +86 13508486908; Email: huchunh5829@126.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • Oncology Department，Second Xiangya Hospital of Central South University
      • Contact: Chunhong Hu, professor; Phone Number: +86 13508486908; Email: huchunh5829@126.com
      • Contact: Fang Wu, professor; Phone Number: 13574858332; Email: wufang4461@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Clinically confirmed advanced NSCLC patients with long-term benefit after first-line immunotherapy

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Advanced NSCLC patients with long-term benefit after first-line immunotherapy (Tumor-informed group); The ctDNA detection will be performed using a tumor-informed analysis approach. This method requires the availability of tumor tissue samples or a fixed-panel next-generation sequencing (NGS) test.	Diagnostic test: ctDNA detection; High-depth sequencing method is used to detecting ctDNA.
Advanced NSCLC patients with long-term benefit after first-line immunotherapy (Tumor-agnostic group); The ctDNA detection will be performed using a tumor-agnostic analysis. This method does not require tumor tissue samples or an NGS testing panel, or in cases where tissue samples are available but fail to meet quality control standards.	Diagnostic test: ctDNA detection; High-depth sequencing method is used to detecting ctDNA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	The duration from study enrollment to disease progression or death, whichever occurs first.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation of ctDNA and risk of progression	The correlation of ctDNA and risk of progression during the erolled observation process	3 years
Lead time	Lead time defined as the interval between ctDNA detection and imaging of progression.	3 years
Incidence of adverse events	the incidence of adverse events during the whole observation time	3 years
Overall survival (OS)	Overall survival (OS) defined as the duration from study enrollment until death due to any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is defined as the proportion of study participants who achieve complete response (CR) or partial response (PR) among the total study participants.	3 years
Factors influencing ctDNA detection	Analyze the factors affecting ctDNA shedding and non-shedding.	3 years
Differences between ctDNA MRD and other peripheral blood biomarkers.	Differences between ctDNA MRD and other peripheral blood biomarkers.	3 years

Collaborators and Investigators

• Sponsor: Fang Wu
• Collaborators: Zhejiang Cancer Hospital; Xiangya Hospital of Central South University; Sun Yat-sen University; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Fujian Cancer Hospital; Second Affiliated Hospital, School of Medicine, Zhejiang University; First Affiliated Hospital Xi'an Jiaotong University; Guizhou Provincial People's Hospital; The Third Xiangya Hospital of Central South University; The First Affiliated Hospital of Guangzhou Medical University; ZhuZhou Central Hospital; Wuhan Union Hospital, China; Hunan Province Tumor Hospital; Zhejiang Provincial People's Hospital; Inner Mongolia People's Hospital; Loudi Central Hospital; Yueyang Central Hospital; Third Affiliated Hospital of Third Military Medical University; Qinghai Province Tumor Hospital; Zhangjiajie Affiliated Hospital of Hunan Normal University; Chang Sha First Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: January 1, 2022
• First Submitted That Met QC Criteria: January 15, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: ctDNA; advanced lung cancer; long-term benefit; minimal residual disease (MRD); first-line immunotherapy; the risk of progression
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Disease Progression; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: XYEYY20211024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No