Lung Cancer (NSCLC)
Conditions
Brief summary
This is a single-center randomized trial that investigates microwave ablation (MWA) combined with EGFR-TKI therapy in 120 early-stage NSCLC patients (T1-T2N0M0, EGFR-mutant) unsuitable for standard treatments. Participants are stratified by tumor characteristics and randomized equally to MWA alone, MWA-TKI concurrent, or TKI induction followed by MWA-TKI, assessing disease-free survival, overall survival, and safety outcomes. The study compares the clinical benefits and optimal sequencing of local ablation with targeted therapy in early-stage EGFR-mutant NSCLC management.
Detailed description
This is a single-center, randomized, controlled, exploratory study enrolling patients with mixed ground-glass or solid lesions on CT, histologically or cytologically confirmed as NSCLC, harboring EGFR mutations, and clinically staged as Ia, Ib, or IIa (size ≤5 cm, T1-T2N0M0). Patients deemed unsuitable for or refusing surgery/radiotherapy after multidisciplinary assessment were included. Eligible participants who provided informed consent were randomized in a 1:1:1 ratio into three groups: microwave ablation alone (MWA), MWA combined with targeted therapy (MWA-TKI), or targeted therapy induction followed by MWA combined with targeted therapy (TKI-MWA-TKI). Randomization was stratified by solid tumor proportion (\<50% vs ≥50%), tumor size (8-30 mm vs \>30 mm), and EGFR mutation status (Ex19del vs Ex21 L858R). The study aims to enroll 120 participants. The primary endpoints include disease-free survival (DFS), overall survival (OS), and the incidence of adverse events. The study evaluates the efficacy, safety, and clinical benefits of MWA combined with EGFR-TKI therapy in early-stage NSCLC, comparing different treatment sequences.
Interventions
DEVICEMWA
Enrolled participants undergo microwave ablation (MWA) after comprehensive assessment of lesion location, size, and individual condition. CT or other imaging modalities are used to monitor changes in the ablation zone. The puncture needle is appropriately distributed within the lesion based on its morphology, and ablation duration is determined by imaging-confirmed coverage of the lesion. All procedures are performed under general anesthesia. Ablation time, power, and cycles are recorded intraoperatively, with continuous ECG monitoring throughout. Immediate post-procedure chest CT or other imaging is performed to document intraoperative complications (e.g., pneumothorax, bleeding). Participants are routinely observed for 24 hours post-procedure, followed by CT re-examination and documentation of any complications.
DRUGTKI
1. Study Drug: Furmonertinib (Shanghai Allist Pharmaceuticals Co.,Ltd.); 2. Administration: Oral, 80 mg once daily. In the MWA-TKI group, targeted therapy is initiated post-MWA if no significant complications occur, continuing for up to 24 months without severe toxicity. In the TKI-MWA-TKI group, a 3-month induction with Furmonertinib is followed by CT re-evaluation; if no contraindications are present, MWA is performed, and targeted therapy resumes post-procedure, continuing for up to 21 months without severe toxicity.
Sponsors
Shanghai Allist Pharmaceuticals Co.,Ltd.
Shanghai Chest Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* CT findings showing mixed ground-glass or solid lesions, histologically or cytologically confirmed as NSCLC, with clinical stages Ia, Ib, or IIa (size ≤5 cm, T1-T2N0M0) according to the 9th edition of TNM classification. * EGFR exon 19 deletion or exon 21 L858R mutation. * Age ≥18 years. * ECOG PS score of 0-2. * Expected survival ≥3 months. * Deemed unsuitable for or refusal of surgery/radiotherapy after multidisciplinary discussion. * No prior EGFR-TKI targeted therapy. * Willing to undergo initial ablation therapy, with good compliance to examinations and follow-ups, and able to understand the study and provide informed consent.
Exclusion criteria
* Severe liver, kidney, heart, lung, or brain dysfunction or other comorbidities that preclude tolerance to MWA or targeted therapy. * Chest CT findings indicating percutaneous inaccessibility of the lung lesion for MWA. * Platelet count \<50×10⁹/L, severe bleeding tendency, or uncorrectable coagulation disorders. * Current or prior (within 3 months) use of anti-tumor drugs or EGFR-TKI therapy. * Uncontrolled conditions (including but not limited to non-pulmonary malignancies, active infections, symptomatic congestive heart failure, unstable angina, arrhythmias, psychiatric disorders, etc.). * Pregnant or breastfeeding women, or those planning pregnancy during the study. * Other conditions deemed by the investigator as unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3-year disease-free survival (DFS) rate in the MWA-TKI and TKI-MWA-TKI groups | From the time of treatment to the time of disease progression or death, assessed up to 3 year | The proportion of subjects who remain free from disease recurrence or death from the start of treatment until 3 years post-treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1-year and 2-year disease-free survival (DFS) rates in the MWA-TKI and TKI-MWA-TKI groups | From the time of treatment to the time of disease progression or death, assessed up to 1 year or 2 year | The proportion of subjects who remain free from disease recurrence or death from the start of treatment until 1year post-treatment or 2 years post-treatment. |
| 1-year, 2-year, and 3-year overall survival (OS) rates in the MWA-TKI and TKI-MWA-TKI groups | From the time of treatment to the time of death, assessed up to 1 year, 2 year and 3 year. | The proportion of subjects who remain alive from the start of treatment until 1 year, 2 years, and 3 years post-treatment. |
| Overall survival (OS) in the MWA-TKI and TKI-MWA-TKI groups | From the time of treatment to the time of death, assessed up to 5 year. | The time from the start of treatment to the subject's death or the last follow-up. |
| 1-year, 2-year, and 3-year disease-free survival (DFS) rates in the MWA group. | From the time of treatment to the time of disease progression or death, assessed up to 1 year, 2 year or 3 year. | The proportion of subjects who remain free from disease recurrence or death from the start of treatment until 1 year, 2 years, and 3 years post-treatment. |
| 1-year, 2-year, and 3-year overall survival (OS) rates in the MWA group | From the time of treatment to the time of death, assessed up to 1 year, 2 year and 3 year. | The proportion of subjects who remain alive from the start of treatment until 1 year, 2 years, and 3 years post-treatment. |
| Overall survival (OS) in the MWA group | From the time of treatment to the time of death, assessed up to 5 year. | The time from the start of treatment to the subject's death or the last follow-up. |
| The incidence of adverse events (AEs) | 24 months after treatment | AEs include procedure-related adverse reactions during or after MWA and drug-related adverse reactions caused by targeted therapy. |
| Exploration of potential predictive biomarkers and synergistic effects of MWA combined with targeted therapy | Disease progression or up to 2 years (whichever occurs first) | By comparing pre- and post-treatment tumor biopsy specimens, peripheral blood samples, and bronchoalveolar lavage fluid samples, this study investigates changes in local lesions and the systemic microenvironment, including biomarkers, metabolites, and the immune microenvironment, and their relationship with efficacy and prognosis. Additionally, potential regulatory pathways are explored. Furthermore, by comparing the three groups, the study examines whether MWA combined with targeted therapy can produce synergistic effects, whether these effects are related to the timing of targeted therapy, and the underlying regulatory mechanisms of such synergy. |
Contacts
Primary ContactFangfang Xie, MD
Backup ContactJiayuan Sun, MD, PHD
Outcome results
None listed