REGORAFENIB for Arteriovenous malformations

Inclusion criteria

• {"criterion_text":"- Inclusion is limited to adults aged at least 18 years old: 1. Patients with complex and symptomatic fast-flow vascular malformations that are refractory to standard care (surgery and/or embolization) with progression and life-threatening disease (Shobinger classification III et IV). They have to present pain as the predominant complaint with Visual Analogic Scale (VAS>4), not alleviated with standard painkiller, including morphinic derivatives.\n- 2. Patients must have adequate bone marrow function: hemoglobin> 10,0 g/dl, neutrophils >1.500/mm³ and platelets > 100.000/mm³.\n- 3. Patients must have the following laboratory values: • Total serum bilirubin ≤ 1.5 x ULN (or totally bilirubin ≤3 x ULN with direct bilirubin ≤ 1.5 x ULN in patients with well documented Gilbert Syndrome) • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (or < 5.0 x ULN if hepatic metastases are present) • Serum creatinine < 1.5 x ULN. If the serum creatinine is ≥ 1.5 x ULN, then a 24-hour Creatinine Clearance must be conducted and the result must be ≥ 60 mL/min.\n- 4. ECOG score 0-1\n- 5. Patients previously treated with sirolimus, alpelisib, trametinib or thalidomide could be included\n- 6. Patients able to swallow.\n- 7. Negative urine pregnancy test in women of childbearing potential (WOCBP) with sexual relations.\n- 8. WOCBP (participant or non-participant partner) agree to use highly effective contraceptive method during treatment and for 8 weeks after stopping regorafenib.\n- 9.Male (participant or non-participant partner) agree to use mandatory condom during the treatment duration and for 8 weeks after stopping regorafenib"}

Exclusion criteria

• {"criterion_text":"- As AVM can result in impaired cardiac function, congestive heart failure is allowed if stabilized. 1. New York Heart Association functional classification Grade 3-4 congestive heart failure should be excluded from this study, but remains at the discretion of the investigator as regorafenib could indirectly improve cardiac function by controlling AVM. Other significant cardiac diseases, including unstable angina pectoris, ventricular arrhythmia, valvular disease with documented compromise in cardiac function, myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function, family history of congenital long or short QT, or known history of QT/QTc prolongation of Torsades de Pointes (TdP) are excluded from this trial.\n- 2. Impairment of Gastro-Intestinal (GI) function or GI disease that may significantly alter the absorption of regorafenib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea ≥ Grade 2, malabsorption syndrome, or small bowel resection)\n- 3. Known hypersensitivity to drugs or metabolites from similar classes as study treatment.\n- 4. Patient has (an)other concurrent severe and /or uncontrolled medical condition(s) that would, in the investigator’s judgement, contraindicate participation in the clinical study (e.g. acute or chronic pancreatitis, liver cirrhosis, active chronic hepatitis, severely impaired lung function with a spirometry ≤ 50% of the normal predicted value and/or O2 saturation ≤ 88% at rest, etc.)\n- 5. Immunocompromised patients, including known seropositivity for HIV\n- 6. Pregnant or lactating women"}

Primary endpoints

• {"endpoint_text":"- The efficacy assessment of regorafenib will be based on these following criteria : 1) Quality of life questionnaire adapted from OVAMA questionary with self-perception of improved quality of life (in %)\n- 2) Evaluation of symptoms focused on pain.\n- 3) Size of the lesion on the basis of clinical evaluation and the 12-month doppler ultrasonography, MRI and arteriography.","definition_or_measurement_approach":"1) Quality of life: measured using an OVAMA-adapted questionnaire with self-perception of improved quality of life reported as percentage; 2) Symptoms/pain: evaluation focused on pain (baseline VAS>4 at inclusion) and symptom assessment; 3) Lesion size: measured by clinical evaluation and imaging (12-month Doppler ultrasonography, MRI and arteriography)."}

Secondary endpoints

• {"endpoint_text":"- A secondary endpoint will explore the efficacy of regorafenib based on Functional limitation. The evaluation of functional limitation (difficulties in performing any action of everyday life) based on a scale ranging from 0 (no limitation) to 10 (excessive limitation).","definition_or_measurement_approach":"Functional limitation assessed on a 0 (no limitation) to 10 (excessive limitation) scale evaluating difficulty performing activities of daily living."}

Belgium

Earliest CTIS Part Ii Submission Date

08-04-2025

Latest Decision Or Authorization Date

12-08-2025

Processing Time Days

126

Number Of Sites

1

Number Of Participants

10

Primary sponsor

Full Name

Cliniques Universitaires Saint-Luc

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium

Third parties

• {"country":"","full_name":"Bayer SA-NV","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Cliniques universitaires Saint-Luc","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Novitan","duties_or_roles":"Monetary support","organisation_type":""}