Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC

Study Overview
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Brief Summary
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This clinical trial aims to explore the minimal residual disease (MRD) status of early NSCLC after curative surgery and the clinical outcomes of adjuvant chemotherapy. Next-generation sequencing technique will be used to examine the circulating tumor DNA (ctDNA) from MRD of 150 postoperative patients with stage IB-IIA NSCLC who received adjuvant chemotherapy.

Detailed Description
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Minimal residual disease (MRD) refers to the small number of malignant cells that remain after curative treatments (curative intent surgical resection, radiotherapy, and/or chemotherapy). MRD is common in patients with blood cancer, and is known to be associated with recurrence and poor prognosis. Recent studies also reported that MRD-negative in postoperative solid tumors such as colorectal/colon cancer and breast cancer is associated with better survival outcomes. However, the clinical values of MRD monitoring for adjuvant therapy in postoperative NSCLC remain inadequate. Circulating tumor DNA (ctDNA), a type of cell-free DNA, refers to the DNA fragments that are derived from tumor cells and circulate in the blood. Recently, next-generation sequencing (NGS) was successfully applied to monitor NPM1, RUNX1 and FLT3 mutations in multiple myeloma. Thus, NGS technique is a promising tool for sensitive MRD monitoring, which provides the ctDNA profiling from MRD, and then provides future decision-making treatment for postoperative NSCLC patients. Thus, this clinical study aims to monitor the ctDNA status of MRD, and to explore the clinical value of MRD monitoring in decision-making adjuvant therapy for patients with stage IB-IIA NSCLC after curative surgery. A total of 150 patients with primary curable stage IB-IIA NSCLC will be recruited in this clinical trial. The following samples will be collected from each patient including 1) preoperative blood samples; 2) surgical tissue samples; 3) blood samples 3-7 days after surgery; 4) blood samples every 3-6 month during adjuvant chemotherapy; and 5) white blood control samples. In addition, demographic and tumor characteristics of the patients will be collected for subsequent analysis, including age, sex, tumor stage, pathological stage, disease couse time, PS score, etc. NGS will be used to analyze the whole exons of potential driver genes to obtain the MRD status. Statistical analyses will be performed to analyze the survival outcomes of MRD-positive and MRD-negative group and to explore the clinical value of MRD monitoring for adjuvant therapy in postoperative NSCLC.

Official Title
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Utility of ctDNA In Predicting Whether Giving Adjuvant Chemotherapy In Patients With Stage IB-IIA Resected Non-small Cell Lung Cancer: A Prospective Cohort Study

Conditions
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Carcinoma, Non-Small-Cell Lung, Next-Generation Sequencing, Chemotherapy, Adjuvant, Neoplasm, Residual, Circulating Tumor DNA

Intervention / Treatment
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* Drug: Adjuvants, Pharmaceutic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged between 18 and 70 years Histological diagnosis of primary NSCLC Patients received curative surgery for primary NSCLC Tumor stage IB-IIA after curative-intent surgical resection ECOG score: 0-1 Participant is willing to use an acceptable form of contraception during the study. Participant is willing and able to give informed consent for participation in the study. Exclusion Criteria: The patient has received neoadjuvant therapy, including radiotherapy and chemotherapy, targeted therapy and immunotherapy Patients are unwilling or unable to receive the curative-intent resection Patients have or have had history of malignant tumor Patients who suffer from severe uncontrolled disease that require systemic treatment or considered unsuitable for participating this trial due to other reasons by the investigator Patients with severe gastrointestinal dysfunction, cardiac dysfunction, interstitial lung disease, etc. Laboratory test results showed inadequate bone marrow or organ function Blood transfusion during or within 2 weeks before the surgery History of alcohol abuse or drug overdose Pregnant or breastfeeding women Patients who are currently or have participated in any other anti-tumor clinical trials Inadequate baseline data, such as preoperative and postoperative blood samples (Lack of 2 consecutive blood test or a total of 3 blood samples), surgical tumor tissues, and ctDNA test.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MRD-positive Cohort<br>ctDNA positivity in pretreatment and posttreatment plasma samples was defined by accessing the presence of one or more mutations identified in match tumor samples. A mutation was considered present when at least one consensus read contained the mutation and passed the local polishing pipeline. The MRD positive cohort was randomly divided into two groups, one group for interventional treatment and the other group for observation. | Drug: Adjuvants, Pharmaceutic<br>* Patients with stage IB-IIA NSCLC after curative surgery were treated with adjuvant chemotherapy. The blood samples of the patients before and after adjuvant chemotherapy will be collected to examine the MRD status<br>* Other names: adjuvant chemotherapy;|
| MRD-negative Cohort<br>ctDNA negative in pretreatment and posttreatment plasma samples was defined by accessing the presence of no mutation identified in match tumor samples. According to the clinical prognostic characteristics of the MRD negative group, the clinician decides to observe or treat. | Drug: Adjuvants, Pharmaceutic<br>* Patients with stage IB-IIA NSCLC after curative surgery were treated with adjuvant chemotherapy. The blood samples of the patients before and after adjuvant chemotherapy will be collected to examine the MRD status<br>* Other names: adjuvant chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year DFS rate | DFS defined as the time from randomization to occurrence of any of the following events, whichever occurs first: Locoregional recurrence or distant metastases as determined by an independent central radiology assessment. Occurrence of the second primary (same or other) cancer as determined by an independent central radiology assessment. Death from any cause. Loss to follow-up is censored. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ctDNA status | Change of Circulating tumor DNA (ctDNA) status (every 3 months) | Through study completion, up to 5 years | 
| TEAE | Occurrence of treatment emergent adverse event (TEAE) | Through study completion, up to 3 years | 
| IMP | Occurrence of dose reduction and discontinuation of IMP due to a TEAE | Through study completion, up to 3 years | 
| Overall survival | Follow-up of the patients will be conducted to analyze 3-year and 5-year overall survival | 3 years and 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, next-generation sequencing, adjuvant chemotherapy, minimal residual disease, circulating tumor DNA