Trametinib in neurofibromatosis type 1 related symptomatic plexiform neurofibromas

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)1 site in 1 country30 target enrollmentSeptember 6, 2024

DrugsGSK1120212B Mekinist 0.5 mg film-coated tablets

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Not specified
Sponsor: Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Enrollment: 30
Locations: 1
Primary Endpoint: Tumor volume on volumetric MRI analysis
Status: Not yet recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

To determine whether trametinib can induce shrinkage in plexiform neurofibromas. Response to treatment is defined as a tumor volume decrease from baseline of at least 20%, monitored by using volumetric MRI analysis.

Registry

euclinicaltrials.eu

Start Date

September 6, 2024

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Responsible Party

Principal Investigator

Christine Noordhoek

Scientific

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Eligibility Criteria

Inclusion Criteria

•Patient with (mosaic) NF1
•Normal hematological function: Hemoglobin (Hb)≥6 mmol/l, absolute neutrophil count (ANC)≥1.5x109/l, and platelets≥100x109/l
•Normal hepatic function: bilirubin <1.5x the upper limit of normal (UNL), unless gilbert then: bilirubin <3xUNL and AST/ALT <5xUNL
•Normal renal function: creatinine <1.5xUNL
•Patients with a clinically significant symptomatic plexiform neurofibroma (PNF), such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions. This will be determined by the treating physician.
•Signed, written informed consent
•Age: 18 or higher
•Karnofsky performance level of ≥70%
•No standard treatment options = inoperable PNF PNF that cannot be surgically completely removed without risk for substantial morbidity due to invasiveness, high vascularity or encasement of, or close proximity to, vital structures of the PNF.
•At least one measurable PNF, defined as a well-demarcated lesion of at least 3 cm measured in one dimension.

Exclusion Criteria

•Prior treatment with MEK inhibitor(s)
•Risk factors for gastrointestinal perforation, including history of diverticulitis, metastases to the gastrointestinal tract and concomitant use of medications with a recognized risk of gastrointestinal perforation
•Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses, or renal transplant, including any patient known to have hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) will be excluded.
•Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.
•Any serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with subject’s safety
•Known severe hypersensitivity to trametinib or any excipient of trametinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to trametinib
•Pregnant, lactating or actively breastfeeding female subjects
•Inability to undergo MRI and/or contraindication for MRI examinations
•History of a malignancy within 5 years of inclusion, except squamous cell carcinoma of the skin, cervical premalignant lesions and other curatively treated malignancy
•Prior radiotherapy less than 6 weeks prior to enrollment

Outcomes

Primary Outcomes

Tumor volume on volumetric MRI analysis

Secondary Outcomes

Numeric pain rating scale (NRS-11)
Pain interference (PROMIS)
QLQ-SF36
Medical photography
Adverse events according to CTCAEv5.0
Time to first significant progression defined as >20% volumetric growth of the index lesion(s)
Incidence of surgical interventions