lung cancer
Conditions
Interventions
Experimental group:Neoadjuvant therapy with icotinib combined with bevacizumab
Sponsors
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences.
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1) Able to provide written informed consent and understand and comply with the requirements and assessment schedule of the study. 2) Aged between 18 and 80 years (inclusive). 3) Must have a histopathological diagnosis of lung adenocarcinoma obtained via "bronchoscopy" or "CT-guided biopsy of the primary lung lesion." 4) Confirmed by cytology or histology as EGFR gene exon 19 and/or 21 sensitive mutations (without T790M mutation) stage IB-IIIA lung adenocarcinoma (8th edition AJCC), with staging definitions as follows: Stage IB: Defined as a primary tumor with maximum diameter >3 cm, or 2-3 cm in diameter but involving the visceral pleura. Stage IIA: Defined as cT2bN0. Stage IIB: Defined as cT1a-cN1, cT2a-bN1, or cT3N0. Stage IIIA: Defined as cT1a-cN2, cT2a-bN2, cT3N1, or cT4N0-1. N2: Defined as imaging or pathological confirmation of mediastinal lymph node metastasis, expected to be resectable. Imaging-defined lymph nodes with short diameter >10 mm or multiple fused lymph nodes locally. Clinical staging can be used to determine patient eligibility, but it is recommended that N2 patients undergo endobronchial ultrasound or mediastinoscopy to document lymph node involvement. If archived tumor tissue is available, tumor samples and pathology reports of baseline samples are required for biomarker analysis. 5) Standard lung lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy must be performed according to lung cancer treatment guidelines; wedge resection or segmentectomy is not allowed. 6) Systematic pulmonary hilar and mediastinal lymph node dissection must be performed according to guidelines, regardless of preoperative mediastinal staging. For right-sided resection, at least lymph nodes at levels 2R, 4R, 7, 8, and 9 must be cleared. For left-sided resection, at least lymph nodes at levels 4L, 5, 6, 7, 8, and 9 must be cleared. If pulmonary lymph nodes have been cleared but not listed in the pathological report, it does not affect subsequent enrollment or data analysis. 7) The investigator must assess at least one measurable lesion according to RECIST 1.1 criteria. 8) ECOG performance status 0 or 1. 9) Adequate bone marrow and organ function, with laboratory indicators meeting the following criteria: Absolute Neutrophil Count (ANC) =1.5 × 10^9/L; Platelets =100 × 10^9/L; Hemoglobin >9 g/dL; Total bilirubin =1.5 × upper limit of normal (ULN) or total bilirubin >ULN but direct bilirubin =ULN; Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) =2.5 × ULN; Serum creatinine =1.5 × ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) =60 ml/min; Coagulation function is adequate, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) =1.5 × ULN. 10) For women of childbearing potential, a negative urine or serum pregnancy test must be obtained within 7 days prior to the first administration of the study drug. If the urine pregnancy test cannot confirm a negative result, a blood pregnancy test is required. Women not of childbearing potential are defined as postmenopausal for at least 1 year, or those who have undergone surgical sterilization or hysterectomy. 11) All subjects (regardless of gender) must use highly effective contraception during the entire treatment period and for 120 days after the last dose of the study drug if there is a risk of pregnancy.
Exclusion criteria
Exclusion criteria: 1) Previous receipt of any antitumor treatment, including EGFR-TKI therapy, anti-angiogenesis therapy, radiotherapy/chemotherapy, biological therapy, immunotherapy, or experimental treatments. 2) EGFR sensitive mutations with T790M mutation or EGFR rare mutations such as EGFR 20ins, G719X, L861Q, S768I, or other non-classical mutations. 3) Prior lung segmentectomy or wedge resection, and/or absence of lymph node dissection. 4) T4 tumors invading the aorta, esophagus, and/or heart; and/or any large-volume N2 disease. Tumors showing invasion of major vessels on imaging (CT or MRI) or those judged to have a high likelihood of invading major vessels and causing potentially fatal hemorrhage during the study period. 5) Previous interstitial lung disease, drug-induced interstitial lung disease, or any clinically evidenced active interstitial lung disease; or baseline CT scan showing idiopathic pulmonary fibrosis. 6) Diagnosis of malignancies other than non-small cell lung cancer within 2 years prior to first drug administration (excluding treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or treated carcinoma in situ). 7) Any unstable systemic disease, including: active infection, uncontrolled hypertension, unstable angina, angina that started within the last 3 months, congestive heart failure (= NYHA class II), myocardial infarction (within 6 months prior to enrollment), severe arrhythmia requiring medication, liver, kidney, or metabolic diseases. 8) Histopathological results showing squamous cell carcinoma, small cell carcinoma, large cell neuroendocrine carcinoma, or sarcomatoid carcinoma components. 9) Known allergy or hypersensitivity to any components of icotinib or bevacizumab. 10) Known human immunodeficiency virus (HIV) infection. 11) A history of clear neurological or psychiatric disorders, including epilepsy or dementia. 12) Pregnant or breastfeeding women. 13) Other conditions that, in the opinion of the investigator, make the patient unsuitable for inclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Major pathologic response rate, MPR;Event-free survival, EFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR;Pathologic complete response rate, pCR;R0 resection rate;Pathological downstaging rate;Disease-free survival, DFS;Overall survival, OS; | — |
Countries
China
Contacts
Public ContactNaixin Liang
Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences.
Outcome results
None listed