Leflunomide Treatment for MEN1 Patients - the LUMEN1 Trial

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05605587

Studienbeginn:
Mai 2023

Letztes Update:
02.06.2023

Wirkstoff:
Leflunomide 20 mg

Indikation (Clinical Trials):
Multiple Endocrine Neoplasia Type 1

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
University Hospital, Basel, Switzerland

Collaborator:
-

Kontakt

Julie Refardt, MD
Kontakt:
Phone: +41615565618
E-Mail: julie.refardt@usb.ch» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Unispital Basel
4053 Basel
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Julie Refardt
Phone: +41615565618
E-Mail: julie.refardt@usb.ch» Ansprechpartner anzeigen

Studien-Informationen

Brief Summary:

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder due to mutations

in the tumor suppressor gene MEN1 with the corresponding gen product menin. MEN1 is

characterized by the occurrence of parathyroid, pancreatic islet and anterior pituitary

tumors which can release excessive amounts of hormones (= functional active tumors). Other

tumors (e.g. carcinoid tumors, adrenocortical tumors, meningiomas, facial angiofibromas,

collagenomas, lipomas) have also been described. There is no geno-phenotype correlation but

the disease occurs after a second hit of the corresponding gene within the endocrine organ

leading to an uncontrolled growth.

MEN1-patients have a decreased life expectancy, mainly due to pancreatic neuroendocrine

tumors (pNETs) which are often multiple and more aggressive than in non-MEN1 patients. To

date, no prophylactic treatment exists to prevent tumor development in this hereditary

disease.

Leflunomide has been used as a treatment for rheumatoid arthritis for many years. It is a

potent inhibitor of the dihydroorotate dehydrogenase (DHODH). According to some preclinical

studies, leflunomide showed antineoplastic activities in several malignancies, including

prostate, breast, bladder, multiple myeloma, leukemia, and lymphoma. A recent study

identified an interaction between MEN1 mutation and DHODH inhibition. In this study,

leflunomide selectively killed MEN1 deficient cells in vitro, prevented the occurrence of

pancreatic tumor development in xenograft models and led to tumor regression / stabilisation

in three MEN1 patients with advanced aggressive pancreatic neuroendocrine tumors.

Accordingly, leflunomide could be used as a new treatment option for patients with known MEN1

germline mutation and associated endocrine disease. The aim of this study is, therefore, to

evaluate the antitumor effect of leflunomide treatment on MEN1-associated tumors in patients

with known MEN1-syndrome.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Adult (≥18 years) patients with known pathogenic or likely pathogenic MEN1-germline

mutation and at least 1 associated tumor lesion OR hormonal syndrome

Exclusion Criteria:

- uncontrolled arterial hypertension, defined as blood pressure >160/100 mmHg

- Impaired kidney function, defined as creatinine clearance <50ml/min

- Impaired liver function, defined as bilirubin or liver transaminases >3 times upper

normal range

- Cytopenia, defined as one or several of the following: hemogloin <100 g/l, leucopenia

<2x109/l, thrombocytopenia <100x109/l

Studien-Rationale

Primary outcome:

1. The primary outcome is the effect of a 6 months' treatment with leflunomide 20mg/day on MEN1-associated functional and non-functional tumors (Time Frame - 6 months)

Geprüfte Regime

Leflunomide 20 mg:
once daily for 6 months

Quelle: ClinicalTrials.gov

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