Monocentric Pilot Trial evaluating the safety and efficacy of Regorafenib in Arterio-Venous Malformations that are refractory to standard care

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cliniques Universitaires Saint-Luc

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Decision date (initial)

2025-04-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bayer SA-NV · Cliniques universitaires Saint-Luc · Novitan

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

*To confirm the safety of regorafenib in patients with AVM and long-term tolerability; *To evaluate the efficacy of regorafenib on signs and symptoms caused by AVMs that are refractory to standard care; *To evaluate whether regorafenib treatment can alleviate signs and symptoms caused by these complex vascular anomalies that are refractory to standard care

Secondary objectives 1

1. To evaluate : *whether regorafenib could reduce volume of the malformation on a long-term follow-up ; *whether patients with this rare disorder will see their quality of life improved

Conditions and MedDRA coding

Arterio-Venous Malformations

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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. 2. Patients must have adequate bone marrow function: hemoglobin> 10,0 g/dl, neutrophils >1.500/mm³ and platelets > 100.000/mm³. 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. 4. ECOG score 0-1 5. Patients previously treated with sirolimus, alpelisib, trametinib or thalidomide could be included 6. Patients able to swallow. 7. Negative urine pregnancy test in women of childbearing potential (WOCBP) with sexual relations. 8. WOCBP (participant or non-participant partner) agree to use highly effective contraceptive method during treatment and for 8 weeks after stopping regorafenib. 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 1

1. 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. 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) 3. Known hypersensitivity to drugs or metabolites from similar classes as study treatment. 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.) 5. Immunocompromised patients, including known seropositivity for HIV 6. Pregnant or lactating women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 %) 2) Evaluation of symptoms focused on pain. 3) Size of the lesion on the basis of clinical evaluation and the 12-month doppler ultrasonography, MRI and arteriography.

Secondary endpoints 1

1. 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).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cliniques Universitaires Saint-Luc

Sponsor organisation

Cliniques Universitaires Saint-Luc

Address

Hippokrateslaan 10, Batiment 54 Batiment 54

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

Cliniques Universitaires Saint-Luc

Contact name

Dr Emmanuel Seront

Public contact point

Organisation

Cliniques Universitaires Saint-Luc

Contact name

Dr Emmanuel Seront

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications