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Selumetinib in teens with plexiform neurofibromas

Safety and efficacy of Selumetinib in adolescents with NF1 related plexiform neurofibromas (PN)


This study is for patients diagnosed with Neurofibromatosis Type 1 (NF1) and inoperable Plexiform Neurofibromas (PN) tumors that grow along the nerves. The reason for the study is to find out if taking selumetinib with food affects the blood levels and side-effects of this medicine in adolescent children with this disease.

Who May Qualify?:


  • Age 12 to <18 years
  • With a diagnosis of NF1 and inoperable plexiform neurofibromas and one other criterion:
    • Six or more café-au-lait macules (≥ 0.5cm in prepubertal participants or ≥ 1.5cm in post pubertal participants)
    • Freckling in axilla or groin
    • Optic glioma
    • Two or more Lisch nodules
    • A distinctive bone lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
    • A first degree relative with NF1
  • That may develop significant complications from inoperable PN
  • Who have had prior treatment with any MEKi (including Selumetinib)
  • Who meet certain Karnofsky performance level standards
  • With a BSA ≥ 1.3 and ≤ 2.5 m2
  • Who are able to swallow whole capsules
  • Who are willing to take part in all treatment periods 
  • Who are on a stable, highly-effective course of contraception, if sexually active
  • Who are not pregnant
Who Does Not Qualify:

Patients with:

  • Evidence or suspicion of optic glioma, malignant glioma, MPNST, or other cancer requiring treatment with chemotherapy or radiation therapy
  • Prior malignancy requiring active treatment (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the participant had been disease free for ≥ 2 years or which would not have limited survival to < 2 years).
  • A life-threatening illness, medical condition, organ system dysfunction of laboratory finding which, in the Investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of selumetinib, or put the study outcomes at undue risk.
  • Clinically significant cardiovascular disease as defined by the following:
    • Known inherited coronary disease;
    • History of angina or acute coronary syndrome
    • Symptomatic heart failure - New York Association Class II to IV
    • Prior or current cardiomyopathy
    • Severe valvular heart disease
    • Current or history of atrial fibrillation
    • Baseline LVEF below LLN or < 55% measured by ECHO or cardiac MRI
    • A QTcF > 450 ms
    • Blood pressure > 95% percentile for age, height and gender measured as described in Appendix F.
  • Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses, or renal transplant, including any participant known to have hepatitis B, hepatitis C, or HIV will be excluded. Participants with HIV who have adequate CD4 count, not requiring antiretroviral medication, may be enrolled.
  • Liver function tests: bilirubin > 1.5 × the ULN for age (with the exception of those with Gilbert syndrome) or AST/ALT > 2 × upper limit of normal.
  • Renal Function: Creatinine clearance or radioisotope glomerular filtration rate < 30 mL/min/1.73 m2 or a serum creatinine > 1.2 mg/dL (for participants aged between 12 and 15 years) or > 1.5 mg/dL for participants aged > 15 years).
  • Participants with the following ophthalmological findings/conditions:
    • Current or past history of RPED/CSR or RVO;
    • Intraocular pressure >21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP). Participants with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after discussion with the Medical Monitor.
    • Participants with any other significant abnormality on ophthalmic examination should be discussed with the Sponsor for potential eligibility.
    • Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or longstanding orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study.
  • Refractory nausea and vomiting, chronic GI diseases (eg, inflammatory bowel disease), or significant bowel resection that would adversely affect the absorption/bioavailability of the orally administered study medication.
  • Any unresolved chronic toxicity, associated with previous therapy for NF1-PN:
    • Gastrointestinal toxicity of CTCAE Grade 1 or higher.
    • Any other unresolved chronic toxicity with CTCAE Grade ≥ 2, except hair changes (such as alopecia or high lightening).
  • Participants who have previously been treated with a MEKi (including selumetinib) and either discontinued treatment or required a dose reduction due to toxicity
  • Recent major surgery within a minimum of 4 weeks prior to starting study intervention, with the exception of surgical placement for vascular access. Have planned major surgery during the treatment period.
  • Inadequate haematological function: defined as an absolute neutrophil count < 1500/μL, Hb < 9g/dL, and platelets < 100,000/μL or have required a blood or platelet transfusion or received growth factors within the 7 days prior to the start of study intervention.

Study Status:
Study Sponsor:

AstraZeneca AB

Full IRB Study Title:
A Phase I, Single-Arm, Sequential Study to Evaluate the Effect of Food on the Gastrointestinal Toxicity and Pharmacokinetics of Selumetinib after Multiple Doses in Adolescent Children with Neurofibromatosis Type 1 (NF1) Related Plexiform Neurofibromas (PN)
IRB Study ID:
If you are interested in this study or have questions about your child's eligibility, please contact:

Showers Family Center for Childhood Cancer and Blood Disorders. 330-543-8730

Lead Investigator
Erin Wright, MD

Director, Neuro-Oncology; Director, Shannon E. Wilkes Targeted Therapy Program; Co-Director, Neurofibromatosis Clinic; Pediatric Neuro-Oncologist
Pediatric Brain Tumor ProgramShowers Family Center for Childhood Cancer and Blood DisordersNeurofibromatosis (NF) Clinic

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