NSCLC
Conditions
Interventions
intervention group:Safe introduction period: 6 subjects were enrolled, with ivermectin at 20mg/kg every 3 weeks + third-generation EGFR TKI every day
Expansion enrollment period: 30 subjects were enro
Sponsors
Shandong First Medical University Affiliated Tumor Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Voluntary signing of a written informed consent form; 2. >= 18 years old; 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 4. Expected survival period >= 3 months; 5. Histological or cytological confirmed, locally advanced (IIIB/IIIC stage) or metastatic (IV stage) non-squamous NSCLC (according to the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer 8th edition lung cancer TNM staging); 6. Before enrollment, confirmed by tumor histology or cytology or hematology that EGFR sensitive mutations are positive, including 19 exon deletion (19Del) and 21 exon point mutation (L858R), and patients with EGFR-T790M mutation can also be enrolled. 7. Occurrence of slow progression or potential progression during EGFR-TKIs treatment: Slow progression definition: EGFR TKIs treatment efficacy reaches complete response (CR) or partial response (PR), and the patient's tumor burden increases by no more than 20% within 6 months (target lesion increase by no more than 20%; and/or no more than 3 new lesions, and/or non-target lesion number increase by no more than 20%), without clinical symptom deterioration. Potential progression definition: Blood CEA = 10 ng/mL (time interval of detection not less than 1 month); or blood CEA >= 10.0 ng/mL, and two consecutive tests gradually increase (time interval not less than 1 month). 8. At least one measurable lesion; 9. Normal major organ function, that is, meeting the following criteria: 1) Blood routine examination must meet (within 14 days, no blood transfusion, no use of hematopoietic factors and no use of drugs to correct): a. Absolute neutrophil count (ANC) >= 1.5 × 10^9/L (1,500/mm^3); b. Platelet count (PLT) >= 90 × 10^9/L (100,000/mm^3); c. Hemoglobin (HB) >= 90 g/L; 2) Biochemical examination must meet the following criteria: a. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) = 28 g/L; c. Serum creatinine sCr <= 1.5 × ULN, (Cockcroft-Gault formula, urine protein < 2+ or 24-hour urine protein quantification < 1.0 g; 3) Coagulation function must meet: international normalized ratio INR <= 1.5 × ULN and activated partial thromboplastin time APTT <= 1.5 × ULN
Exclusion criteria
Exclusion criteria: 1. Patients with large cell carcinoma and mixed cell lung cancer, which contain small cell lung cancer components; 2. Patients who have primary resistance to EGFR-TKIs (the duration of EGFR-TKI treatment is less than 3 months); 3. Patients with brain metastasis and intratumoral hemorrhage who have experienced recurrence after radiotherapy; 4. Patients whose imaging results during the screening period show that the tumor surrounds important blood vessels or has obvious necrosis and cavities, and the investigator determines that participating in the study will cause bleeding risks; 5. Patients currently have hypertension and their systolic blood pressure is >= 150 mmHg or diastolic blood pressure is >= 100 mmHg after oral antihypertensive drug treatment; 6. Patients with uncontrolled hyperglycemia (fasting blood glucose > 15 mmol/L); 7. Patients with severe interstitial pneumonia; 8. Patients with a history of severe bleeding tendency or coagulation dysfunction; if there are significant clinical symptoms of bleeding within 1 month before the first administration, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing or expectoration of >= 1 teaspoon of blood or small blood clots or only hemoptysis without sputum, allowing those with blood in sputum to be enrolled), nasal bleeding (excluding epistaxis bleeding and retrograde nasal bleeding); 9. Unless it is small cell lung cancer, the subjects had other malignant tumors within 3 years before enrollment. Patients with other malignant tumors that have been cured by local treatment, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ, are not excluded; 10. Patients with active autoimmune diseases that require systemic treatment in the past two years (such as treatment with disease-modifying drugs, corticosteroids, immunosuppressants). Alternative treatments (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not considered as systemic treatment; 11. Patients had a significant medical history within 1 year before the first administration, specifically: 1) Within 12 months before the first administration, there was the need for hospitalization for unstable angina pectoris, myocardial infarction, congestive heart failure (NYHA classification >= 2), or vascular diseases (such as aortic aneurysm with rupture risk); there was a history of hypertension crisis or hypertensive encephalopathy. 2) Within 6 months before the first administration, there was a history of esophageal and gastric varices, severe ulcers, wounds not healed, abdominal fistula, abdominal abscess or acute gastrointestinal bleeding; 3) Within 1 month before the first administration, there was any arterial thromboembolic event, grade 3 or above venous thromboembolic events, transient cerebral ischemic attack, cerebral vascular accident, hypertension crisis or hypertensive encephalopathy; 4) Within 4 weeks before the first administration, there was an acute exacerbation of chronic obstructive pulmonary disease; 12. Within 4 weeks before the first administration, patients had a severe infection, including but not limited to those requiring hospitalization for complications, sepsis or severe pneumonia; 13. Within 4 weeks before the first administration, patients had undergone major surgery or suffered from severe trauma, or had a major surgical plan within 4 weeks a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS) ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR);Disease control rate (DCR);Overall survival period (OS);Safety; | — |
Countries
China
Contacts
Public ContactMeng Xiangjiao
Shandong First Medical University Affiliated Tumor Hospital (Shandong Provincial Tumor Hospital)
Outcome results
None listed