Extracranial arteriovenous malformation
Conditions
Interventions
Experimental group:Patients orally took FCN-159 tablets, once daily, continuously for a 28-day cycle.
Sponsors
Shanghai Ninth People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Patients aged =18 years and =65 years. 2. Clinically or radiologically (CTA, MRI, MRA, DSA, color Doppler, etc.) diagnosed extracranial AVMs, including CM-AVMs and sporadic AVMs. 3. Patients who meet one of the following criteria are eligible for enrollment: Patients, as judged by the investigator, unsuitable for surgical or interventional therapy; Patients with recurrence or failure to respond after surgical or interventional therapy Patients with at least one complication (including bleeding, chronic pain, ulcer/necrosis/gangrene, visceral and/or skeletal involvement and/or cardiac dysfunction, malformation, and functional disorders) that requires clinical intervention. 4. Patients with available tissue or peripheral blood samples for central laboratory tests of the following biomarkers, including but not limited to RASA1, EPHB4, BRAF, KRAS, NRAS, MEK (MAP2K1 and MAP2K2) and its other upstream and downstream genes, and HHT-related genes such as PTEN and SMAD4. 5. Patients with Karnofsky Performance Status Score = 50. See Appendix 4 Functional Status Scale/Score. 6. Patients with adequate organ and bone marrow functions (blood component and cell growth factor products are not allowed within 14 days before the Screening): Absolute neutrophil count = 1.0×109/L; Hemoglobin = 9 g/dL; Platelet count = 100×109/L; Serum total bilirubin = 1.5×ULN (upper limit of normal), and = 3.0×ULN for patients with Gilbert's syndrome; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5×ULN; Albumin = 3 g/dL; Creatinine < 1.5×ULN, or creatinine clearance or radioisotope GFR = 50 ml/min/1.73 m2; Coagulation: international normalized ratio (INR) and activated partial thromboplastin time (APTT) = 1.5×ULN; 7. Toxicities from prior AVM treatments recovered to = Grade 1 in CTCAE v5.0 (except for alopecia). 8. Patients will voluntarily sign a written informed consent form. 9. For patients of childbearing potential, they should agree to use highly effective contraceptive methods, i.e., combined hormonal contraception, progesterone-only hormonal contraception associated with ovulation inhibition, intra-uterine device, intra-uterine system, bilateral tubal occlusion, vasectomy of the partner, or sexual abstinence during treatment and for at least 90 days after the last dose of study drug. Male patients should agree to avoid donating sperm for at least 90 days after the last dose.
Exclusion criteria
Exclusion criteria: 1. Patients diagnosed with hereditary hemorrhagic telangiectasia (HHT), PTEN hamartoma tumor syndrome (PHTS), or CLOVES syndrome. 2. Patients previously treated with one of the followings: a. Drug therapy for AVMs within 4 weeks or 140 mmHg or diastolic blood pressure (DBP) > 90 mmHg, as shown on repeated measurements under current anti-hypertensive therapy. 8. Dysphagia, active digestive diseases, malabsorption syndrome, or other conditions that affect the absorption of the study drug. 9. Previous or current retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED), glaucoma, and other significant ophthalmologic findings. 10. Interstitial pneumonia, including clinically significant radiation pneumonitis. 11. Patients with cardiac functions or comorbidities which meet one of the following conditions will be excluded: a. Mean QTcF > 470 msec, as calculated from three 12-lead electrocardiograms (ECGs) using the QTcF formula of the instrument at the study site during the Screening; patients with risk factors for QTcF prolongation, such as uncorrectable hypokalemia, hereditary long QT syndrome; or on medications that prolong QTcF interval (mainly class Ia, Ic, III antiarrhythmics). For drugs with the potential to prolong QTcF interval, see Appendix 10 Drugs That Possibly Prolong QTc Interval. b. New York Heart Association (NYHA) Functional Classification = Class 3 congestive heart failure; c. Clinically significant arrhythmias, including but not limited to complete left bundle branch conduction abnormality; d. Known clinically significant concomitant coronary artery disease, cardiomyopathy, and severe valvular disease; e. Left ventricular ejection fraction (LVEF) 1000 IU/ml or meeting the study site's diagnostic criteria for active hepatitis B infection), hepatitis C (hepatitis C virus RNA positive), or human immunodeficiency virus infection (HIV positive). 13. Pregnant or breastfeeding women. Patients who become pregnant during the study should be withdrawn. 14. Known allergy to the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR by Digital Subtraction Angiography (DSA); | — |
Secondary
| Measure | Time frame |
|---|---|
| Flow rate and impedance by Color Doppler Flow Imaging(CDFI);ORR by Nuclear Magnetic Resonance Imaging (MRI);Clinical outcome; | — |
Countries
China
Contacts
Public ContactXiaoxi Lin
Shanghai Ninth People's Hospital
Outcome results
None listed