Neurofibromatosis type 1, NF1, plexiform neurofibroma
Conditions
Interventions
Trametinib 2mg daily, orally, continuous until progression, patients refusal to continue the medication with trametinib or unacceptable side effects of trametinib.
Sponsors
Erasmus MC
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patient with (mosaic) NF1 2. 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. 3. Signed, written informed consent 4. Age: 18 or higher 5. Karnofsky performance level of =70% 6. 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. 7. At least one measurable PNF, defined as a well-demarcated lesion of at least 3 cm measured in one dimension. 8. Able to swallow and retain orally administered medication. 9. Female Subjects of Childbearing Potential must have negative pregnancy test within 7 days prior study treatment and agrees to use highly effective contraception 10. Normal hematological function: Hemoglobin (Hb)=6 mmol/l, absolute neutrophil count (ANC)=1.5x109/l, and platelets=100x109/l 11. Normal hepatic function: bilirubin <1.5x the upper limit of normal (UNL), unless gilbert then: bilirubin <3xUNL and AST/ALT <5xUNL 12. Normal renal function: creatinine <1.5xUNL
Exclusion criteria
Exclusion criteria: 1. Prior treatment with MEK inhibitor(s) 2. Inability to undergo MRI and/or contraindication for MRI examinations 3. History of a malignancy within 5 years of inclusion, except squamous cell carcinoma of the skin, cervical premalignant lesions and other curatively treated malignancy 4. Prior radiotherapy less than 6 weeks prior to enrollment 5. Prior major surgery less than 4 weeks prior to enrollment 6. An investigational agent within the past 30 days. 7. Enzyme-inducing anticonvulsants, anti-coagulants (including platelet aggregation inhibitors) or other prohibited medication(s) or requirement for prohibited medications 8. 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. 9. 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 10. 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 11. 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. 12. Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption. 13. Any serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with subject’s safety 14. 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 15. Pregnant, lactating or actively breastfeeding female subjects
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate | — |
Secondary
| Measure | Time frame |
|---|---|
| Patient reported outcomes of pain and disability and quality of life The effect of trametinib on disfigurement. Adverse events reporting according to CTCAEv5.0 Time to first significant progression defined as >20% volumetric growth of the index lesion(s) Incidence of surgical interventions | — |
Contacts
Public ContactWalter Taal
Erasmus MC Cancer Institute
Outcome results
None listed