This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Leflunomide Treatment for MEN1 Patients - the LUMEN1 Trial (LUMEN1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05605587
Recruitment Status : Recruiting
First Posted : November 4, 2022
Last Update Posted : June 2, 2023
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
MEN1 Gene Mutation Drug: Leflunomide 20 mg Not Applicable

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Leflunomide Treatment for MEN1 Patients - the LUMEN1 Trial
Actual Study Start Date : May 2, 2023
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Leflunomide

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Leflunomide 20mg Drug: Leflunomide 20 mg
once daily for 6 months


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  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 ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05605587


Contacts
Layout table for location contacts
Contact: Julie Refardt, MD +41615565618 julie.refardt@usb.ch

Locations
Layout table for location information
Switzerland
Unispital Basel Recruiting
Basel, Switzerland, 4053
Contact: Julie Refardt    +41615565618    julie.refardt@usb.ch   
Sponsors and Collaborators
University Hospital, Basel, Switzerland
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT05605587    
Other Study ID Numbers: LUMEN1
First Posted: November 4, 2022    Key Record Dates
Last Update Posted: June 2, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Endocrine Neoplasia Type 1
Multiple Endocrine Neoplasia
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
 Endocrine System Diseases
Leflunomide
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs