A Phase 2 interventional study of Surgery and Osimertinib in Non-Small Cell Lung Cancer and EGFR, sponsored by Jianxing He. Not yet recruiting. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-09-16.
Sponsored by Jianxing He · Phase 2, Interventional, and Treatment
This study is designed to explore whether resecting the primary lung cancer, followed by osimertinib, can improve outcomes for patients with advanced non-small cell lung cancer (NSCLC) harboring sensitizing EGFR mutations (exon 19 deletion or L858R). Patients with stage III-IV NSCLC will be included and randomly assigned to receive either surgery to remove the primary lung cancer followed by osimertinib, or osimertinib alone. All patients will continue treatment until disease progression or they need to stop for another reason. The primary outcome being studied is progression-free survival (PFS). Secondary outcomes include overall survival (OS), objective response rate (ORR), disease control rate (DCR), adverse effects (AEs), serious adverse effects (SAEs) and quality of life (QoL). The findings from this study may help determine whether surgery combined with EGFR tyrosine kinase inhibitor (TKI) provides more benefit than EGFR-TKI alone for patients with EGFR-mutant advanced NSCLC.
Osimertinib is a third-generation EGFR-TKI that has become one of the standard first-line treatments for patients with advanced NSCLC harboring sensitizing EGFR mutations such as exon 19 deletion and L858R substitution. Although osimertinib significantly improves survival outcomes, most patients eventually experience disease progression because of drug resistance, and long-term survival remains limited. Surgical resection has traditionally been reserved for early-stage NSCLC. However, emerging evidence suggests that removing the primary tumor, even in the setting of advanced disease, may help reduce tumor burden, delay resistance, and potentially enhance the effectiveness of systemic therapies. To date, there is little high-quality evidence from randomized trials evaluating the role of primary tumor resection in combination with EGFR-TKI for patients with unresectable stage III-IV NSCLC harboring sensitizing EGFR mutations. This randomized, open-label, phase 2 study is designed to evaluate whether combining primary tumor resection with osimertinib provides superior clinical outcomes compared with osimertinib alone in patients with advanced EGFR-mutant NSCLC. Approximately 118 eligible patients will be randomized in a 1:1 ratio to receive either surgery followed by osimertinib or osimertinib monotherapy. Treatment will continue until disease progression or discontinuation criteria are met. The primary outcome is PFS assessed by independent radiology review according to RECIST v1.1. Secondary outcomes include OS, ORR, DCR, AEs, SAEs and QoL. Statistical analysis will include Kaplan-Meier estimation of median PFS with 95% confidence intervals, log-rank testing for comparing differences between the two treatment groups, and Cox proportional hazards models for calculating hazard ratios. Stratification will be performed based on clinical stage, EGFR mutation type, tumor size, and baseline demographic characteristics. The results of this trial are expected to provide high-level evidence on whether surgery combined with EGFR-TKI offers additional clinical benefit over standard EGFR-TKI alone in advanced EGFR-mutant NSCLC.
6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.
This study's planned enrollment of 118 is above the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →Jianxing He is the lead sponsor of 11 studies on the registry; 6 are open to participants now.
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Adequate organ function, including:
① Hematologic function: absolute neutrophil count ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥9.0 g/dL.
② Hepatic function: ALT and AST ≤2.5 × ULN (≤5 × ULN if liver metastases are present); total bilirubin ≤1.5 × ULN.
③ Renal function: serum creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min (Cockcroft-Gault formula).
Adequate pulmonary function (must meet at least one of the following to ensure postoperative reserve):
① FEV1 ≥1.2 L (or ≥40% of predicted value);
② FEV1/FVC ≥0.7, to exclude severe obstructive ventilatory dysfunction;
③ DLCO (diffusing capacity for carbon monoxide) ≥40% of predicted value, to assess diffusion capacity.
④ If preoperative FEV1 \<1.2 L or DLCO \<40%, additional cardiopulmonary exercise testing (e.g., 6-minute walk test, stair climbing test) is recommended to evaluate postoperative pulmonary reserve.
Exclusion Criteria:
Participants will receive oral osimertinib at a dose of 80 mg once daily, continued until disease progression or the occurrence of unacceptable toxicity.
Drug: Osimertinib
Participants will first undergo cytoreductive surgery. After adequate postoperative recovery for 4-6 weeks, they will receive oral osimertinib at a dose of 80 mg once daily, continued until disease progression or the occurrence of unacceptable toxicity.
Procedure: Surgery · Drug: Osimertinib
① Preoperative evaluation must confirm resectability. Thoracoscopic minimally invasive surgery will be performed, with the surgical approach selected according to disease conditions, such as lobectomy, segmentectomy, wedge resection, or sleeve resection; ② Systematic mediastinal lymph node dissection or lymph node sampling (based on preoperative imaging and intraoperative evaluation) must be performed; ③ Postoperative recovery must be adequate (postoperative complications ≤ Clavien-Dindo grade II).
Dose: 80 mg orally, once daily, until disease progression or the occurrence of unacceptable toxicity. The dose should be administered at approximately the same time each day, at 24-hour intervals.
Progression-free Survival
Progression-free survival is defined as the time from randomization to the first documentation of disease progression or death from any cause, whichever occurs first. Disease progression will be assessed by the Independent Radiology Review Committee according to RECIST version 1.1 criteria.
Time frame: From randomization until the first documentation of disease progression or death from any cause, whichever occurs first (up to 5 years).
Overall Survival
Overall survival is defined as the time from randomization to death from any cause.
Time frame: Randomization to death from any cause (up to 5 years).
Objective Response Rate
The proportion of patients achieving complete and partial remission after treatment, measured according to RECIST v1.1 criteria.
Time frame: Randomization until disease progression or death, which ever occurs first (up to 5 years).
Disease Control Rate
Disease control rate is defined as the proportion of participants with complete response, partial response, and stable disease, as determined by RECIST v1.1 criteria.
Time frame: Randomization until disease progression or death, which ever occurs first (up to 5 years).
Adverse Events
Safety will be assessed by recording treatment-related adverse events (AEs) and serious adverse events (SAEs), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: From randomization to disease progression or death (up to 5 years).
Quality of Life (QoL) evaluated by European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30)
The EORTC QLQ-C30 is a 30 item instrument meant to assess some of the different aspects that define the quality of life of cancer patients (range: 0-100; higher scores indicate better functioning and quality of life).
Time frame: Randomization until disease progression or death, which ever occurs first (up to 5 years).
Quality of Life (QoL) evaluated by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13)
Supplementary lung cancer-specific questionnaire to be used in conjunction with the QLQ-C30 (range: 0-100; higher scores indicate worse lung cancer-related symptoms).
Time frame: Randomization until disease progression or death, which ever occurs first (up to 5 years).
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Plan to share: No
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This study is not yet recruiting, as verified in Sep 2025. You cannot join it, but the record below documents what was studied.
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