Ignite Creation Date:
2024-05-06 @ 6:16 PM
Last Modification Date:
2024-10-26 @ 2:45 PM
Study NCT ID:
NCT05605587
Status:
RECRUITING
Last Update Posted:
2023-06-02
First Post:
2022-11-01
Brief Title:
Leflunomide Treatment for MEN1 Patients - the LUMEN1 Trial
Sponsor:
University Hospital Basel Switzerland
Organization:
University Hospital Basel Switzerland
Study Overview
Official Title:
Leflunomide Treatment for MEN1 Patients - the LUMEN1 Trial
Status:
RECRUITING
Status Verified Date:
2023-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LUMEN1
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 eg 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
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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None