Adjuvant Target Therapy Guided by ctDNA-MRD in Patients With EGFR-mutant II-IIIA Non-small Cell Lung Cancer (ECTOP-1022)

Adjuvant Target Therapy Guided by ctDNA-MRD in Patients With EGFR-mutant II-IIIA

This study plans to conduct ctDNA testing on EGFR mutation-positive stage II-IIIA (N1-N2) NSCLC patients after radical surgery (R0 resection). Patients with positive ctDNA testing will receive standard treatment according to clinical guidelines, while patients with negative ctDNA testing will be assessed based on comprehensive clinical and pathological characteristics. After receiving or not receiving standard adjuvant chemotherapy, patients will be randomly assigned in a 1:1 ratio to either the observation follow-up group (experimental group) or the osimertinib adjuvant treatment group (control group). The aim is to explore whether observation follow-up for patients with negative ctDNA after surgery has a prognosis non-inferior to osimertinib treatment, and to investigate the disease-free survival rate of EGFR mutation-positive stage II-IIIA (N1-N2) NSCLC patients with positive ctDNA after surgery receiving osimertinib adjuvant treatment, providing more precise treatment guidance for adjuvant therapy in this specific type of NSCLC patients with EGFR mutation-positive tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Cancer; Minimal Residual Disease; EGFR Gene Mutation
• Intervention / Treatment: Drug: No adjuvant therapy; Drug: Osimertinib

• Study Type: Interventional
• Enrollment (Estimated): 226
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age greater than 18 years old, both males and females are eligible.
2. Histologically confirmed diagnosis of non-small cell lung cancer.
3. Diagnosis of stage II-IIIA (N1-N2) non-small cell lung cancer based on the 8th edition TNM staging guidelines combined with radiological evaluation.
4. EGFR mutation-positive status confirmed through molecular testing (such as ARMS-PCR or high-throughput sequencing), specifically with mutations 19del or 21L858R.
5. Able to undergo R0 surgical resection.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-1. Expected survival of more than 12 months.

7. Baseline blood routine and biochemical indicators meeting the following criteria:

   • Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L;
   • Lymphocyte count ≥ 0.5 × 10^9/L;
   • Platelet count ≥ 100 × 10^9/L;
   • Hemoglobin ≥ 9 g/dL.
   • Total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
   • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 times ULN.
8. Patients must provide informed consent, either directly or through their legally authorized representatives, after being informed about the study.

Exclusion Criteria:

1. Pathological diagnosis of mixed-type lung cancer (including a history of small cell lung cancer or non-adenocarcinoma).
2. Received anti-tumor therapy before surgery (including radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.).
3. Rx, R1, R2 surgical resection.
4. Received blood transfusion during surgery or within 2 weeks before surgery.
5. Pregnant or lactating female patients.
6. History of other malignant tumors within the past 5 years, except for cases where other malignant tumors have been cured solely through surgery with a disease-free interval of at least 10 years, curable basal cell carcinoma of the skin, and cervical carcinoma in situ.
7. Any unstable systemic diseases (including active infections, uncontrolled hypertension, unstable angina pectoris, congestive heart failure, myocardial infarction within the past year, severe arrhythmias requiring medication, liver, kidney, or metabolic diseases).
8. Evidence of any other diseases, neurological or metabolic functional disorders, physical examination findings, or laboratory findings that would place the subject at high risk of treatment-related complications.
9. Other factors deemed by the investigators to potentially affect the study process.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: ct-DNA-positive patients receiving no adjuvant osimertinib	Drug: No adjuvant therapy; No adjuvant therapy
Experimental: ct-DNA-positive patients receiving adjuvant osimertinib	Drug: Osimertinib; Adjuvant osimertinib for three years after radical surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The 3-year Disease-Free Survival (DFS) rate between the observation group and the osimertinib treatment group.	Disease-Free Survival	3 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: March 14, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Neoplasm, Residual; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: ECTOP-1022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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