Extracranial arteriovenous malformation
Conditions
Interventions
Experimental group:FCN-159 tablets
Specifications: 1.0 mg/tablet and 4.0 mg/tablet
Adolescent patients 12-18 receive FCN-159 5mg/m^2 up to a maximum of 8mg/day
Adult patients receive FCN-159 8mg orally once daily for a 28-day treatment cycle until disease progression, intolerable toxicity, clinical inbenefit as judged by the investigator, end of the study, o
Sponsors
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Eligibility
Sex/Gender
All
Age
12 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. >=12 years of age and = 50% ( age >= 16 ); or Lansky performance level of >=50% ( age =1.0 × 10^9/L; Hemoglobin >=90 g/L; Platelets >=100 × 10^9/L; Total bilirubin =3 g/dL; Creatinine =50 mL/min; Urine protein = 2+, 24-hour urine protein quantification must be <=1 g. Coagulation function: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) <=1.5 × ULN. 9. Recovery of any toxic reactions from prior AVM treatments to =CTCAE Version 5.0 Grade 1 level (excluding toxicities that do not affect the safety of the medication, such as hair loss, as assessed by the investigator). 10. The patient must voluntarily sign a written informed consent form. 11.For patients of childbearing potential: agreement to use effective contraception methods, such as hormonal combination contraceptives, progesterone-only contraceptives associated with ovulation suppression, intrauterine devices (IUDs), bilateral tubal ligation, partner vasectomy, or abstain from sexual intercourse during treatment and for at least 90 days after the last dose of study treatment. Male patients must agree to avoid sperm donation for at least 90 days after the last dose.
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria are not eligible to participate in this clinical study: 1. Diagnosed with hereditary hemorrhagic telangiectasia (HHT), PTEN hamartoma tumor syndrome (PHTS), or CLOVES syndrome (CLOVES). 2. Previously received one of the following treatments : a. Medication for AVM within 4 weeks prior to the study drug treatment start or less than 5 half-lives of the drug (whichever is shorter). b. Radiation therapy, surgical treatment, or interventional embolization within 4 weeks before study drug treatment. c. Participation in other interventional clinical trials within 4 weeks before study drug treatment. d. Prior use of MEK1/2 inhibitors. 3. Rapid lesion expansion leading to severe functional impairment or life-threatening conditions that require surgical or interventional embolization. 4. History of malignant tumors, excluding curatively treated non-melanoma basal cell carcinoma, ductal carcinoma in situ, or cervical carcinoma in situ within the past 3 years. 5. Inability to undergo MRA or contraindications for MRA (e.g., prosthetics or braces that interfere with volume analysis of target lesions). 6. Inability to undergo DSA or contraindications for DSA (e.g., contrast agent allergy, coagulopathy). 7. Uncontrolled stable hypertension: repeated measurements suggest systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg, despite antihypertensive treatment. 8. Swallowing Difficulties: Presence of dysphagia, active gastrointestinal disease, malabsorption syndrome, or other conditions affecting drug absorption. 9. Oral mucositis of grade>= 3 (severe pain: affects oral eating) or recurrent oral mucositis of grade>= 2 (moderate pain or ulcer: does not affect oral eating, requires dietary adjustment) occurred within 6 months prior to enrollment. 10. History of retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED), glaucoma, or other significant abnormal findings in eye examinations. 11. Interstitial Lung Disease: Including clinically significant radiation pneumonitis. 12. Cardiac Function or Comorbid Conditions: One or more of the following conditions: a. QTcF >470 milliseconds based on the average of three 12-lead ECG measurements during the screening period, or presence of risk factors for QTcF prolongation (e.g., inability to correct hypokalemia, congenital long QT syndrome). b. New York Heart Association (NYHA) classification =2 for congestive heart failure. c. Clinically significant arrhythmias, including but not limited to complete left bundle branch block. d. History of myocardial infarction, coronary artery disease, unstable angina, or cardiomyopathy within 6 months prior to enrollment. e. Left ventricular ejection fraction (LVEF) 1000 IU/ml or meeting the diagnostic criteria for active hepatitis B infection), hepatitis C (positive hepatitis C virus RNA),
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR);Duration of response (DOR);The mean reduction of target lesion volume at 6 months and 12 months evaluated;The average reduction rate of lesions at 6 months and 12 months assessed ;Changes of maximum arterial flow velocity and impedance in target lesion area from baseline detected ;Changes in patient clinical signs and symptom scores from baseline;Safety metrics;Disease Control Rate (DCR);Progression-free survival (PFS);DOR rate for 1 year;PFS rate at 1 year; | — |
Countries
China
Contacts
Public ContactXiaoxi Lin
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Outcome results
None listed