Non-small cell lung cancer
Conditions
Interventions
Dose A :Ametinib 55 mg each time (once a day) and icotinib 125 mg each time (3 times a day)
Dose B:Ametinib 110 mg each time (1 time a day) and Icotinib 125 mg each time (3 times a day)
no:ametinib at a dose of 55 or 110 mg (once a day) and icotinib at a dose of 125 mg (3 times a day)
Sponsors
West China Hospital,Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: (1) Sign the informed consent form voluntarily; (2) The age at the time of signing the informed consent form greater than 18 years old; (3) Patients with stage IV non-small cell lung cancer diagnosed by histopathology or cytology; (4) Patients with asymptomatic brain metastases or symptomatic brain metastases are stable after treatment; (5) The diagnosis of brain metastasis is diagnosed by imaging examinations such as computerized tomography (CT) or nuclear magnetic resonance (MRI); (6) The detection of tumor tissue samples revealed sensitive EGFR mutations and no tyrosine kinase inhibitors targeting EGFR have been used; (7) The ECOG physical status scoring standard within 2 weeks before the first use of the study drug 0-1; (8) The expected life span greater than 3 months; (9) According to the RECIST 1.1 standard, imaging tests show that there are measurable tumor lesions in the brain and extracranium; (10) Laboratory inspection indicators meet the following standards: Neutrophil count >= 1.5x10^9/L; Platelet count >= 100x10^9/L; Hemoglobin >= 90 g/L; Creatinine clearance rate <= 1.5 ULN; The AST and ALT of patients with liver metastases <= 5 ULN, and the AST and ALT of patients without liver metastases <= 2.5 ULN; Total bilirubin <= 1.5 ULN. (11) Women of childbearing age: Appropriate contraceptive measures should be taken from screening to 3 months after stopping the study treatment and should not be breast-feeding. Before starting the administration, the pregnancy test is negative, or meeting one of the following criteria proves that there is no risk of pregnancy: Postmenopausal is defined as amenorrhea at least 12 months after the age is over 50 years and all exogenous hormone replacement therapy is stopped. For women younger than 50 years old, if the amenorrhea is 12 months or more after stopping all exogenous hormone treatments, and the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) are within the reference range of postmenopausal laboratory, they can also Think it is postmenopausal. Have undergone irreversible sterilization, including hysterectomy, bilateral ovarian resection, or bilateral fallopian tube resection, except for bilateral fallopian tube ligation. Male patients: Barrier contraception (ie, condoms) should be used from screening to 3 months after the study treatment is stopped.
Exclusion criteria
Exclusion criteria: (1) Currently participating in other studies or receiving other anti-tumor treatments within 4 weeks of receiving the first treatment. The patient must have recovered from the relevant treatment and previous treatment-related adverse reactions to within CTCAE level 1; (2) Have received any of the following treatments: Have used any EGFR tyrosine kinase inhibitor treatment in the past; The patient had undergone major surgery within 4 weeks before the first administration of the study drug; Have received more than 30% bone marrow irradiation or received extensive radiotherapy within 4 weeks before the first administration of the study drug; Within 7 days before the first administration of the study drug, CYP3A4 strong inhibitors, inducers, or drugs with a narrow therapeutic window that are CYP3A4 sensitive substrates have been used. (3) Patients with a history of other malignant tumors within 5 years. (4) Spinal cord compression, unless asymptomatic and stable, and steroid therapy is not required for at least 2 weeks before the first dose of study treatment. (5) As judged by the investigator, there are any serious or poorly controlled systemic diseases, such as poorly controlled hypertension, active bleeding-prone constitution, or active infection. (6) Refractory nausea, vomiting or chronic gastrointestinal diseases, inability to swallow study drugs or having undergone extensive bowel resection may affect the full absorption of amitinib or icotinib. (7) Meet any of the following cardiac examination results: The average corrected QT interval (QTc) obtained from the resting state of the electrocardiogram (ECG) > 470 msec, and the Fridericia formula is used for QT interval correction (QTcF); Resting ECG suggests that there is a rhythm that requires clinical intervention, conduction or ECG morphological abnormalities (such as complete left bundle branch block, 3 degree atrioventricular block, 2 degree atrioventricular block, and PR interval> 250 msec); There are any factors that increase the risk of QTc prolongation or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death or prolonged QT interval of immediate family members under 40 years old Any combination of drugs in the period; Left ventricular ejection fraction (LVEF) <=40%. (8) A history of interstitial lung disease, a history of drug-induced interstitial lung disease, a history of radiation pneumonitis requiring steroid therapy, or any evidence of clinically active interstitial lung disease. (9) Women who are breastfeeding or whose blood or urine pregnancy test results are positive within 3 days before the first administration of the study treatment. (10) Plan to become pregnant during pregnancy or breastfeeding, or within 120 days from the screening period to the last use of the drug. (11) There is a history of hypersensitivity to any active or inactive ingredients of Ametinib or Icotinib or to drugs with similar chemical structure or the same category as Ametinib or Icotinib. Patients who are judged by the investigator who may not comply well with the procedures and requirements of the study. (12) Any serious or uncontrolled eye disease may increase the safety risk of the patient by the judgment of the doctor. (13) Patients who may have poor compliance with the research procedures and requirements after the investigator's judgment. (14) The investigator judges th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose;Number and proportion of patients who can complete 6 treatment cycles; | — |
Secondary
| Measure | Time frame |
|---|---|
| progression-free survival;overall survival;disease control rate;objective response rate;duration of Response;intracranial progression-free survival;intracranial disease control rate;intracranial objective response rate;intracranial duration of Response;adverse event; | — |
Countries
China
Contacts
Public ContactHuang Meijuan
West China Hospital,Sichuan University
Outcome results
None listed