Clinical trial NCT06709274: Minimal Residual Disease Guiding Adjuvant Therapy in Stage I NSCLC
Official title: Minimal Residual Disease (MRD)-Guided Adjuvant Therapy in Stage I Non-Small Cell Lung Cancer: A Prospective, Multicenter, Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Guangdong Association of Clinical Trials
Sponsor class: OTHER
Collaborators: name: Nanjing Geneseeq Technology Inc.
First posted: 2024-11-29
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This investigator-initiated study aims to evaluate the effectiveness of minimal residual disease (MRD) as a biomarker for guiding adjuvant therapy decisions in patients with Stage I non-small-cell lung cancer (NSCLC). The study will compare outcomes between an MRD-guided management group and a standard-of-care group, focusing on whether the use of MRD information can improve the 3-year disease-free survival rate compared to existing treatment protocols. Participants in the MRD-guided management group will receive targeted therapy, immunotherapy, or observation based on their postoperative MRD status, while those in the standard-of-care group will receive treatments or observation according to current clinical guidelines.


Eligibility criteria: Inclusion Criteria:

1. Non-small cell lung cancer (NSCLC) confirmed by histological and/or cytological examination. Invasive subtypes are required for adenocarcinomas.
2. Stage IA or IB after surgery based on pathological TNM8 staging criteria established by the International Union Against Cancer/American Joint Committee on Cancer (8th Edition).
3. Completely surgical resection (R0) of the primary NSCLC via lobectomy, segmentectomy, or sleeve lobectomy. The gross tumor must be entirely removed, and all surgical margins of the excised tumor must be negative.
4. Complete recovery from surgery with no evidence of disease progression within 2 weeks prior to the first treatment decision.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
6. Minimum life expectancy of ≥12 weeks.
7. Demonstrate adequate organ function, including:

   Hematological parameters:
   * Absolute neutrophil count ≥1.5×10\^9/L
   * Platelet count ≥100×10\^9/L
   * Hemoglobin ≥90 g/L

   Liver function:
   * ALT ≤2.5× upper limit of normal (ULN)
   * AST ≤2.5×ULN
   * Total Bilirubin (TBL) ≤1.5×ULN Renal function: Creatinine level ≤1.25×ULN, or creatinine clearance ≥60 mL/min (measured or calculated using the Cockcroft-Gault formula).
8. Male or female, age between 18 and 75 years.
9. Written informed consent must be obtained from the subject or their legal representative.
10. Participants regardless of sex must agree to use effective contraception during the study period and for 3 months following treatment completion.
11. Willingness and ability to comply with visit schedules, treatment plans, and laboratory assessments.

Exclusion Criteria:

1. Histopathologically confirmed small cell carcinoma components.
2. Presence of multiple pulmonary nodules.
3. Incomplete resections (R1/R2) or resections via bilateral lobectomy, pneumonectomy, or wedge resection.
4. A history of any systemic anti-tumor treatment, including but not limited to surgery, neoadjuvant chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
5. Significant allergies to any targeted drugs, immunotherapies, or chemotherapy agents used in the study.
6. Previous use of any traditional Chinese medicine with anti-tumor properties, or use of such medicine within 2 weeks prior to surgery.
7. History of other malignancies within the past 5 years, with the exception of the following:

   * Other malignancies fully cured by surgery with a disease-free survival of more than 10 years
   * Curable basal cell carcinoma of the skin
   * Bladder carcinoma in situ
   * Cervical carcinoma in situ
8. History of interstitial lung disease, drug-induced interstitial lung disease, radiation-induced pneumonia requiring steroid treatment, or any evidence of clinically active interstitial lung disease.
9. Active hepatitis B, defined as HBsAg positive with an HBV-DNA copy number exceeding the ULN established by the study center, accompanied by abnormal liver function, or requiring treatment as evaluated by the investigator.
10. Presence of any unstable systemic disease, including but not limited to active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the past 3 months, serious arrhythmias that requires medication, liver disease, kidney disease, or metabolic disorders.
11. Evidence of any other diseases, neurological or metabolic disorders, or physical exam or laboratory findings that may suggest contraindications for the investigational drug, or a high risk for treatment-related complications.
12. Any of the following cardiac conditions:

    * Resting ECG QT interval (QTc) \> 470 msec.
    * Significant abnormalities in rhythm, conduction, or morphology on resting ECG, including complete left bundle branch block, third-degree atrioventricular block, or second-degree atrioventricular block
    * Factors increasing the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death in a first-degree relative under the age of 40, or use of medications known to prolong QT interval.
13. Blood transfusion within 2 weeks prior to and during the surgery.
14. History of alcohol or drug abuse.
15. Pregnant or breastfeeding females.
16. Any other factors that the investigator deems may affect the progress of the study or compromise the trial data

Primary outcomes:
measure: 3-Year disease-free survival (DFS) Rate
timeFrame: 3 years post randomization
Secondary outcomes:
measure: 5-Year disease-free survival (DFS) Rate
timeFrame: 5 years post randomization
measure: 5-Year overall survival (OS) rate
timeFrame: 5 years post randomization
measure: Disease-free survival (DFS)
timeFrame: Up to 8 years post randomization
measure: Overall survival
timeFrame: Up to 8 years post randomization
measure: Quality of Life (QoL) Assessed using the EORTC QLQ-C30 (Version 3.0)
timeFrame: Up to 8 years post randomization
measure: Quality of Life (QoL) Assessed using the EORTC QLQ-LC13
timeFrame: Up to 8 years post randomization
Other outcomes:
Locations:
city: Dongguan
country: China
facility: Dongguan People's Hospital
state: Guangdong
city: Foshan
country: China
facility: The First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hostpital
state: Guangdong
city: Guangzhou
country: China
facility: ZhuJiang Hospital of Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Nanning
country: China
facility: The Second Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: The Third People's Hospital of Chengdu
state: Sichuan
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Yi-Long Wu, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangdong Provincial People's Hospital
name: Xue-Ning Yang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: