ctDNA-MRD in Stage IIIB-C NSCLC Patients Treated With Induction Chemoimmunotherapy

The Role of Dynamic Circulating Tumor DNA-Molecular Residual Disease (ctDNA-MRD) Testing in Stage IIIB-C Oncogene-negative NSCLC Patients Treated With Induction Chemoimmunotherapy in the Multidisciplinary Team (MDT) Model of Diagnosis and Treatment

The goal of this observational study is to explore whether ctDNA-MRD dynamic monitoring can more effectively predict the therapeutic effect of induction chemoimmunotherapy followed by surgery or non-surgical treatment for stage IIIB-C driver-negative NSCLC in the MDT model, so as to accurately guide clinical diagnosis and treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Diagnostic test: NGS and ctDNA-MRD detection

Detailed Description

This study is a single-center, observational, non-interventional, prospective study. 50 patients diagnosed with stage IIIB-C driver-negative NSCLC receiving induction chemoimmunotherapy will be planned to be enrolled in the study. Pre-treatment biopsy tissues of enrolled patients will be collected for next-generation sequencing (NGS) of institutionally-developed 1021-gene panel, and personalized detection panel will be customized based on NGS testing results. Patients will be received induction chemoimmunotherapy followed by surgery or non-surgical treatment in the MDT model and ctDNA-MRD testing will be performed at prespecified time points. For patients who received surgery following induction therapy, peripheral blood will be collected in baseline, 1 day before the third cycle of neoadjuvant therapy, 1 day before surgery, 3 days after surgery and landmark time and pulmonary venous blood will be collected intraoperatively. For patients who received non-surgical treatment following induction therapy, peripheral blood will be collected in baseline, 1 day before the third cycle of neoadjuvant therapy, 1 day before non-surgical therapy and landmark time. All included patients will be regularly followed up for at least 5 years.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Yan Hu, M.D., Ph.D.; Phone Number: 8685296122; Email: yanhu@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Department of Thoracic Surgery, Second Xiangya Hospital of Central South University, China
      • Contact: Yan Hu, M.D., Ph.D.; Email: yanhu@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Potentially resectable stage IIIB-C driver-negative NSCLC patients receiving induction chemoimmunotherapy

Description

Inclusion Criteria:

• Histopathology or cytology confirmed the non-small cell lung cancer
• Age ranging from 18 to 75
• Agree to participate in this study and sign an informed consent form
• Treatment-naive tumor
• Driver gene negativity
• According to the American Joint Committee on Cancer (AJCC) eighth edition of the Lung Cancer Staging Manual, the clinical stage is stage IIIB-C potentially resectable tumor
• The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score is 0-1

Exclusion Criteria:

• Patients who cannot understand the content of the experiment and cannot cooperate, and those who refuse to sign the informed consent form
• Small cell lung cancer
• Driver gene positivity
• Tumor directly invades esophagus, heart, aorta, diaphragm, trachea, or carina, or is considered unresectable even following induction therapy
• Patients with solid organ or blood system transplantation
• Previous use of recombinant cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1), or programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors
• Patients with interstitial lung disease
• Patients with acute or chronic infectious disease
• Pregnant and lactating women
• Patients who have undergone other clinical drug trials

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with stage IIIB-C driver-negative NSCLC receiving induction chemoimmunotherapy	Diagnostic test: NGS and ctDNA-MRD detection; NGS and ctDNA-MRD detection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predicting Progression Free Survival	Ability of dynamic ctDNA-MRD assessment to predict progression-free survival (PFS) in stage IIIB-C driver-negative NSCLC patients receiving induction chemoimmunotherapy followed by surgery or non-surgical therapy	up to 5 years
Predicting pathologic complete response	Ability of dynamic ctDNA-MRD assessment to predict pathologic complete response (pCR) in stage IIIB-C driver-negative NSCLC patients receiving induction chemoimmunotherapy followed by surgery	Up to 1 year
Predicting Overall Survival	Ability of dynamic ctDNA-MRD assessment to predict overall survival (OS) in stage IIIB-C driver-negative NSCLC patients receiving induction chemoimmunotherapy followed by surgery or non-surgical therapy	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR)	The proportion of patients achieved complete or partial remission according to RECIST 1.1 prior to definitive surgery.	Up to 1 year
Adverse events (AEs)	Number of patients experiencing AEs will be recorded. An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 5 years
Perioperative complications rate	Number of patients experiencing perioperative complications will be recorded.	Up to 3 years
Health-related Quality of Life	Health-related Quality of Life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0.	Up to 5 years
Perioperative pain evaluation	Perioperative pain evaluation assessed by a numeric rating scale (NRS). A total of 11 points from 0 to 10 are used to describe the pain intensity. 0 means no pain, the number of points increases when the pain is stronger, and 10 means the most intense pain.	Up to 3 years
Lung cancer-related Quality of Life	Health-related Quality of Life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire in Lung Cancer.	Up to 5 years

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University
• Collaborators: Geneplus-Beijing Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): March 1, 2029
• Study Completion (Anticipated): March 1, 2029

Study Registration Dates

• First Submitted: April 4, 2023
• First Submitted That Met QC Criteria: April 18, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: April 18, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: LYF2023026

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No