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

Primary Purpose

MEN1 Gene Mutation

Status
Recruiting
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Leflunomide 20 mg
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for MEN1 Gene Mutation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Unispital BaselRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Leflunomide 20mg

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
November 1, 2022
Last Updated
May 31, 2023
Sponsor
University Hospital, Basel, Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT05605587
Brief Title
Leflunomide Treatment for MEN1 Patients - the LUMEN1 Trial
Acronym
LUMEN1
Official Title
Leflunomide Treatment for MEN1 Patients - the LUMEN1 Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 2, 2023 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MEN1 Gene Mutation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Leflunomide 20mg
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Leflunomide 20 mg
Intervention Description
once daily for 6 months
Primary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Julie Refardt, MD
Phone
+41615565618
Email
julie.refardt@usb.ch
Facility Information:
Facility Name
Unispital Basel
City
Basel
ZIP/Postal Code
4053
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie Refardt
Phone
+41615565618
Email
julie.refardt@usb.ch

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Leflunomide Treatment for MEN1 Patients - the LUMEN1 Trial

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