NCT05605587: LUMEN1

Leflunomide Treatment for MEN1 Patients - the LUMEN1 Trial

Terminated NA Last updated 27 January 2026

What this trial tests

NA trial testing Leflunomide 20 mg in MEN1 Gene Mutation in 3 participants. Terminated before completion.

Timeline

2 May 2023

Primary endpoint
13 January 2026

13 January 2026

Quick facts

Lead sponsor	University Hospital, Basel, Switzerland
Phase	NA
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	3
Start date	2 May 2023
Primary completion	13 January 2026
Estimated completion	13 January 2026
Sites	1 location across Switzerland

Drugs / interventions tested

• Leflunomide 20 mg — full drug profile →

Conditions studied

• MEN1 Gene Mutation — all drugs for MEN1 Gene Mutation →

Sponsor

University Hospital, Basel, Switzerland

Who can join

18 and older, any sex, with MEN1 Gene Mutation. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Small-molecule agents for cancer immunotherapy.
   Wang F, Fu K, Wang Y, Pan C, et al · · 2024 · cited 41× · PMID 38486980 · DOI 10.1016/j.apsb.2023.12.010
2. DHODH-mediated mitochondrial redox homeostasis: a novel ferroptosis regulator and promising therapeutic target.
   Cao J, Chen X, Chen L, Lu Y, et al · · 2025 · cited 23× · PMID 40716151 · DOI 10.1016/j.redox.2025.103788
3. What value do zebrafish have to anticancer drug discovery?
   Xiao B, Landesman-Bollag E, Feng H. · · 2024 · cited 1× · PMID 38327017 · DOI 10.1080/17460441.2024.2313454