The TRAIN study: Trametinib in neurofibromatosis type 1 related symptomatic plexiform neurofibromas
- Conditions
- benign tumorsNeurofibroma1002929910029209
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 30
1. Patient with (mosaic) NF1
2. Patients with a clinically significant symptomatic plexiform neurofibroma,
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 plexiform neurofibroma. Plexiform
neurofibroma 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 plexiform neurofibroma.
7. At least one measurable plexiform neurofibroma, 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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To determine whether trametinib can induce shrinkage in plexiform neurofibromas<br /><br>lesions. Response to treatment is defined as a tumor volume decreases from<br /><br>baseline of >=20%, monitored by using volumetric MRI analysis</p><br>
- Secondary Outcome Measures
Name Time Method <p>Neurofibromatosis type 1 patients with plexiform neurofibromas derive clinical<br /><br>benefit from trametinib treatment:<br /><br>• Patient reported outcomes of pain and disability and quality of life<br /><br>• The effect of trametinib on disfigurement<br /><br>• Safety and tolerability of trametinib<br /><br>• The duration of response<br /><br>• Incidence of surgical interventions</p><br>