Clinical trial NCT05167604: Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Carcinoma, Non-Small-Cell Lung
Next-Generation Sequencing
Chemotherapy, Adjuvant
Neoplasm, Residual
Circulating Tumor DNA
Keywords: non-small cell lung cancer
next-generation sequencing
adjuvant chemotherapy
minimal residual disease
circulating tumor DNA
Lead sponsor: Tang-Du Hospital
Sponsor class: OTHER
First posted: 2021-12-22
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patents with histologically confirmed primary NSCLC, stage IB-IIA, aged 18-70 years

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 3-year DFS rate
timeFrame: 3 years
Secondary outcomes:
measure: ctDNA status
timeFrame: Through study completion, up to 5 years
measure: TEAE
timeFrame: Through study completion, up to 3 years
measure: IMP
timeFrame: Through study completion, up to 3 years
measure: Overall survival
timeFrame: 3 years and 5 years
Other outcomes:
Locations:
city: Xi'an
country: China
facility: The Second Affiliated The Second Affiliated Hospital of Air Force Medical University (Tangdu Hospital)
state: Baqiao
Study officials:
affiliation: Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University
name: Tao Jiang
role: PRINCIPAL_INVESTIGATOR
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