Advanced NSCLC with EGFR-sensitive mutations and brain metastasis
Conditions
Interventions
Experimental group:Six patients are planned to be enrolled in the safety lead-in phase, with a minimum of 146 patients required for the formal study phase. Vormetinib mesylate 160mg/day orally every 3
Sponsors
Henan Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Subjects voluntarily participate and sign written informed consent; 2. Age>=18 years old, male or female; 3. Histologically or cytologically confirmed advanced non-small cell lung cancer [American Joint Committee on Cancer (AJCC) 9th edition TNM stage IV]; 4. Histology or cytology report issued by a hospital or a third-party testing institution recognized by the national assessment confirmed the presence of EGFR 19Del or L858R mutations, with or without other EGFR mutations; 5. ECOG physical status score of 0-2 points; Subject life expectancy >=12 weeks according to the investigator's judgment; 6. Brain parenchymal metastasis confirmed by CT or MRI, with or without symptoms (judged by the investigator); 7. Patients have at least 1 measurable lesion according to the Efficacy Evaluation Criteria in Solid Tumors (RECIST 1.1); 8. Patients have not received systemic anti-tumor therapy for advanced/metastatic non-small cell lung cancer, including standard chemotherapy, biologic therapy, targeted therapy, immunotherapy, or investigational drug therapy before the start of study drug treatment; Patients who have received adjuvant therapy or neoadjuvant therapy (chemotherapy and/or radiotherapy) are allowed to enroll if there is no progression within 6 months after treatment; For patients who have received local therapy (radiotherapy or pleural perfusion therapy), enrollment is allowed if the lesions within the scope of local treatment are non-target lesions; 9. Organ function level must meet treatment needs: absolute neutrophil (NE) value >=1.5×10^9/L, platelet (PLT) count >=75×10^9/L, hemoglobin (HGB) >=80g/L; Serum total bilirubin (TBIL) =50ml/min. (according to the Cockcroft and Gault formula); 10. Males of reproductive potential or females of childbearing potential must use highly effective methods of contraception (e.g., oral contraceptives, intrauterine devices, sexual desire control, or barrier contraception combined with spermicide) during the course of the trial and continue contraception for 12 months after the end of treatment.
Exclusion criteria
Exclusion criteria: 1. Histologically or cytologically unconclusive diagnosis of non-small cell lung cancer; 2. Subjects with only leptomeningeal metastasis confirmed by MRI and/or positive cerebrospinal fluid malignant cytology, but no brain parenchymal metastasis; 3. Expected to receive other systemic anti-tumor therapy other than this study during the trial; 4. Other malignant tumors or history of other malignant tumors within the past 2 years, except for basal cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast that have been effectively controlled; 5. Serious digestive tract diseases that affect drug intake and absorption, including but not limited to peptic ulcer, inflammatory bowel disease, etc.; 6. Known or suspected allergy to the study drug (fumetinib, anlotinib) or other components of its preparation; 7. Previous treatment with any EGFR-TKI; 8. Long-term use of strong CYP3A4 inhibitors or strong inducers within 7 days before the first dose or during the expected trial period; Within 2 weeks before the first dose or during the expected trial period, the use of traditional Chinese medicine or traditional Chinese medicine preparations with anti-tumor indications is required; 9. Known history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy; or Pulmonary symptoms that are acute or progressive at baseline and are considered unsuitable for enrollment by the investigator or high-risk factors that may cause interstitial lung disease and are not suitable for enrollment; 10. Presence of significant arrhythmias (such as QT prolongation >470ms) or heart failure (left ventricular ejection fraction <50%); 11. Pregnant or lactating women; 12. Patients who are participating in other clinical studies or have participated in other clinical studies within 4 weeks; 13. Other severe acute or chronic medical illness or psychiatric illness or laboratory abnormality that, in the opinion of the investigator, may increase the risk associated with participation in the study or may interfere with the interpretation of the study results; or subjects who may not be able to complete this study or may not be able to comply with the requirements of this study (due to administrative reasons or other reasons).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety(Phase One: Safe Introduction Phase);Progression-Free-Survival(PFS)(Stage Two: Formal Research Phase); | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease Control Rate (DCR) (Phase II: Formal Study Phase);Objective response rate (ORR)(Stage Two: Formal Research Phase);Duration of Response(Stage Two: Formal Research Phase);Safety(Stage Two: Formal Research Phase);12m-PFS(Stage Two: Formal Research Phase);12m-PFS(Stage Two: Formal Research Phase); | — |
Countries
China
Contacts
Public ContactGao Fangfang
Henan Cancer Hospital
Outcome results
None listed