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

Overview

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.

Interventions

• Drug Osimertinib
  80mg daily, for EGFR-positive patients
• Drug Alectinib
  600mg BID, for ALK-rearranged patients
• Drug TORIPALIMAB INJECTION (JS001 ) combine with chemotherapy
  Toripalimab 240mg + Platinum-based chemotherapy (Q3W for 4 cycles), followed by Toripalimab maintenance therapy (240mg Q3W for one year), for EGFR/ALK wildtype patients

Primary outcome measures

• 3-Year disease-free survival (DFS) Rate [Time frame: 3 years post randomization]

Secondary outcome measures (6)

• 5-Year disease-free survival (DFS) Rate [Time frame: 5 years post randomization]
• 5-Year overall survival (OS) rate [Time frame: 5 years post randomization]
• Disease-free survival (DFS) [Time frame: Up to 8 years post randomization]
• Overall survival [Time frame: Up to 8 years post randomization]
• Quality of Life (QoL) Assessed using the EORTC QLQ-C30 (Version 3.0) [Time frame: Up to 8 years post randomization]
• Quality of Life (QoL) Assessed using the EORTC QLQ-LC13 [Time frame: Up to 8 years post randomization]

Eligibility criteria

Inclusion criteria

• Non-small cell lung cancer (NSCLC) confirmed by histological and/or cytological examination. Invasive subtypes are required for adenocarcinomas.
• 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).
• 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.
• Complete recovery from surgery with no evidence of disease progression within 2 weeks prior to the first treatment decision.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
• Minimum life expectancy of ≥12 weeks.
• 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).
• Male or female, age between 18 and 75 years.
• Written informed consent must be obtained from the subject or their legal representative.
• Participants regardless of sex must agree to use effective contraception during the study period and for 3 months following treatment completion.
• Willingness and ability to comply with visit schedules, treatment plans, and laboratory assessments.

Exclusion criteria

• Histopathologically confirmed small cell carcinoma components.
• Presence of multiple pulmonary nodules.
• Incomplete resections (R1/R2) or resections via bilateral lobectomy, pneumonectomy, or wedge resection.
• A history of any systemic anti-tumor treatment, including but not limited to surgery, neoadjuvant chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
• Significant allergies to any targeted drugs, immunotherapies, or chemotherapy agents used in the study.
• Previous use of any traditional Chinese medicine with anti-tumor properties, or use of such medicine within 2 weeks prior to surgery.
• 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
• 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.
• 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.
• 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.
• 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.
• 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.
• Blood transfusion within 2 weeks prior to and during the surgery.
• History of alcohol or drug abuse.
• Pregnant or breastfeeding females.
• Any other factors that the investigator deems may affect the progress of the study or compromise the trial data

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 15 centers

• Dongguan People's Hospital — Dongguan
• The First People's Hospital of Foshan — Foshan
• Guangdong Provincial People's Hostpital — Guangzhou
• ZhuJiang Hospital of Southern Medical University — Guangzhou
• Peking University Shenzhen Hospital — Shenzhen
• Shenzhen People's Hospital — Shenzhen
• The Second Affiliated Hospital of Guangxi Medical University — Nanning
• Guizhou Provincial People's Hospital — Guiyang
• … and 7 more centers

Identifiers

NCT: NCT06709274 · CTONG2301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗