non-small-cell lung cancer
Conditions
Interventions
Intervention group:Participants will receive ensartinib at 225 mg orally once a day taken with or without food and receive head radiotherapy (3Gy/ time, 15-17 times) at the same time. Bevacizumab (5mg
Sponsors
The Second Affiliated Hospital of Chongqing Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed, inoperable locally advanced or metastatic non-small cell lung cancer 2. Patients with prior written reports of tissue or liquid specimens confirmed positive for ALK fusion gene mutations (FISH, Vantana IHC, or NGS next-generation sequencing). 3. Brain parenchymal metastases or meningeal metastases confirmed by MRI/CT with cranial contrast, and intracranial lesions must have at least one measurable lesion = 1cm in diameter according to RANO and RECIST 1.1 criteria, and the lesion has not received radiotherapy. 4. Patients with stable SD disease or partial response PR (nonCR/nonPD) evaluated according to RECIST 1.1 criteria for intracranial efficacy 3 months after receiving ensartinib induction therapy, who have not received any previous ALK inhibitor therapy except for ensartinib. 5. Gender: Male or female; 6. Age: 18-75 years old; 7. ECOG 0-2 points 8. Estimated survival = 12 weeks. 9. Have certain organ system function (no blood transfusion or use of component blood within 14 days prior to testing), defined as follows: Absolute neutrophil count = 1.5×109/L; Platelet = 80×109/L; hemoglobin =9 g/dL; Total bilirubin = 1.5 times the upper limit of normal (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN in the absence of liver metastases, and 5 =× ULN in the case of liver metastases Creatinine = 1.5× ULN. Patients with a creatinine > 1.5× ULN and a creatinine clearance of =50 mL/min calculated using the Cockcroft-Gault formula or a 24-hour urine creatinine clearance of =50 mL/min can still be enrolled. 10. Drug-related toxicities except alopecia should be resolved to Grade 1 or below (CTCAE 5.0 criteria). 11. Willing and able to comply with trial and follow-up procedures. 12. Able to understand the nature of the trial and voluntarily sign a written informed consent document.
Exclusion criteria
Exclusion criteria: 1. Evidence of any concurrent or history of malignancy in the past 5 years (except for clinically cured basal cell or squamous epithelial skin cancer as well as resected gastrointestinal tumor, in situ cervix carcinoma and early prostate cancer under endoscope early). 2. After 3 months of treatment with ensartinib, the patients who were confirmed as CR or PD of intracranial lesions according to the RECIST 1.1 standard. 3. Treatment with other ALK inhibitors before taking ensartinib or at the same time combination therapy with ensartinib. 4. Patients that have previously received treatment with head radiotherapy. 5. Patients that have previously received stem cell transplantation or organ transplantation. 6. Clinically significant, uncontrolled cardiovascular and cerebrovascular diseases, including but not limited to: a. Abnormal QTc interval (>=450 ms) or abnormal electrocardiogram assessed by the clinician to be clinically significant; b. Hypertension that is assessed by the investigator to be poorly controlled (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg) c. Arrhythmia or abnormal cardiac conduction that require drug intervention. d. The occurrence of any of the following conditions within 6 months prior to the first dose: a). Congestive heart failure; b). Cardiomyopathy or myocardial infarction; c). Severe/unstable angina, coronary artery/peripheral artery bypass grafting; d). Cardiovascular and cerebrovascular accidents (including transient ischemic attack). 7. Suffering from swallowing dysfunction, active gastrointestinal diseases or other diseases that significantly affect the absorption, distribution, metabolism and excretion of ensartinib. 8. Active hepatitis B virus (HBV; HBsAg positive, and HBV DNA =500IU/ml or higher than the detection limit of the study center), positive for hepatitis C virus antibody, HIV antibody, and treponema pallidum antibody; 9. Past medical history of Interstitial lung disease(ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD 10. Women of child-bearing potential with a positive serum pregnancy test within 7 days prior to starting treatment, pregnant or breastfeeding women, or patients who are not using adequate contraceptive measures or planning to conceive during the study and for 90 days after the last dose of study medication; 11.Patients who are known to have hypersensitivity to ensartinib or any of its excipients. 12.Patients who need to combine the following drugs during treatment: drugs at risk for prolonged QTc and/or torsive-tip ventricular tachycardia; CYP3A strong inhibitor or strong inducer; 13.Patients who are currently receiving warfarin or any other coumarin derivative anticoagulant therapy. 14. According to the investigator's opinion, patients may have other severe, acute, or chronic medical conditions or mental conditions that may increase the risk associated with participating in the study or may interfere with the interpretation of study results. 15.Patients who are deemed inappropriate by the investigator to have poor compliance, cannot or are unwilling to follow the research and/or follow-up procedures listed in the trial protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progress Free Survival;Intracranial PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Intracranial ORR;Intracranial DCR;Evaluation of brain function and quality of life;Incidence of Adverse Events;Overall Survival; | — |
Countries
China
Contacts
Public ContactZhenzhou Yang
The Second Affiliated Hospital of Chongqing Medical University
Outcome results
None listed