Trametinib in neurofibromatosis type 1 related symptomatic plexiform neurofibromas

Phase 2

Not yet recruiting

• Conditions: Neurofibromatosis type 1

• Registration Number: 2024-516593-30-00
• Lead Sponsor: Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

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.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-09-06
• Last Update Posted: 2024-09-06

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 30

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.

Able to swallow and retain orally administered medication.

Female Subjects of Childbearing Potential must have negative pregnancy test within 7 days prior study treatment and agrees to use highly effective contraception

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

Prior major surgery less than 4 weeks prior to enrollment

An investigational agent within the past 30 days

Enzyme-inducing anticonvulsants, anti-coagulants (including platelet aggregation inhibitors) or other prohibited medication(s) or requirement for prohibited medications

Left ventricular dysfunction, New York Heart Association Class II, III, or IV heart failure, acute coronary syndrome within the past 6 months, clinically significant uncontrolled arrhythmias, and uncontrolled hypertension.

A history of retinal vein occlusion (RVO) or predisposing factors for RVO, including uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Tumor volume on volumetric MRI analysis		Tumor volume on volumetric MRI analysis

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC); 🇳🇱 Rotterdam, Netherlands

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

🇳🇱Rotterdam, Netherlands

Walter Taal

Site contact

0107041415

w.taal@erasmusmc.nl