Official Title
An Intermediate Access Protocol for Selumetinib for Treatment of Neurofibromatosis Type 1 With Inoperable, Progressive/Symptomatic Plexiform Neurofibromas (PN)
Brief Summary

This will be an open-label, single-arm, multicenter intermediate access protocol which provides treatment access to selumetinib for eligible patients with neurofibromatosis type 1 (NF1) who have inoperable, progressive/symptomatic plexiform neurofibromas (PN) without any alternative therapeutic options. All patients will continue to receive drug while they are deriving clinical benefit. Approximately 100 patients in the US will be treated as part of this protocol

Detailed Description

Patients must have received a clinical diagnosis of NF1 and have inoperable,
progressive/symptomatic PN, where inoperable is defined as PN that cannot be surgically
completely removed without risk of substantial morbidity.

The population are patients with NF1 who have inoperable, progressive/symptomatic PN aged ≥
2years with onset of disease before they were 18 years and who have demonstrated an ability
to swallow whole capsules, who have no further treatment options and are not eligible for
clinical trials.

There is no maximum duration for selumetinib treatment. Patients may continue to receive
selumetinib as long as they continue to show clinical benefit, as judged by the treating
physician, and in the absence of unacceptable toxicity.

Once patients have been discontinued from treatment, other available treatment options will
be at the discretion of the physician

Approved for marketing
Intermediate-size Population
NF type1 With Inoperable Plexiform Neurofibromas

Drug: Selumetinib

open-label, single-arm, multicenter intermediate access protocol

Eligibility Criteria

Inclusion Criteria:

1. Diagnosis of neurofibromatosis type 1 (NF1) and have inoperable,
progressive/symptomatic plexiform neurofibromas (PN)

2. Presence of inoperable PN , defined as a PN that cannot be surgically completely
removed without risk for substantial morbidity

3. Patients aged ≥2 with onset of disease before they were 18 years and a BSA ≥ 0.55 m2
who are able to swallow whole capsules. (approx. length 15.4 mm, diameter 5.4 mm). A
swallow test must be performed before requesting drug

4. Normal cardiac function defined as normal ejection fraction (ECHO, MUGA or cardiac
MRI) as per institutional normal and absence of prior heart disease

5. Adequate blood pressure as defined in line with local practice.

6. The patient has exhausted all available approved therapies as appropriate for NF1 with
inoperable progressive/symptomatic PN

7. Provision of a signed informed consent prior to any protocol specific procedures.
Patients already receiving selumetinib through single patient access who enroll in
this protocol must be reconsented and sign the consent form for this intermediate
access protocol.

8. For female patients of childbearing potential, have evidence of a post-menopausal
status, or a negative urinary or serum pregnancy test.

Exclusion Criteria:

1. Unresolved chronic toxicity ≥ CTCAE Grade 2 from previous therapy

2. Patients eligible for any ongoing clinical trials with selumetinib in the indication
in question

3. Ophthalmological conditions: Current or past history of retinal pigment epithelial
detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion
Intraocular pressure (IOP) should not be > 21 mmHg for adults or outside the range of
normal for children or uncontrolled glaucoma (irrespective of IOP)

4. Male or female patients of reproductive potential and, as judged by the investigator,
are not employing an effective method of birth control.

5. Female patients who are breast-feeding.

6. Have evidence of any other significant clinical disorder or laboratory finding that,
as judged by the treating physician, makes it undesirable for the patient to
participate in the study.

7. Have any evidence of a severe or uncontrolled systemic disease (e.g. unstable or
uncompensated respiratory, cardiac, hepatic, or renal disease, active infection
(including hepatitis B, hepatitis C, HIV), active bleeding diatheses or renal

8. Have refractory nausea and vomiting, chronic gastrointestinal diseases (e.g.,
inflammatory bowel disease), or significant bowel resection that would adversely
affect the absorption / bioavailability of the orally administered study medication

Eligibility Gender
Eligibility Age
Minimum: 2 Years ~ Maximum: 130 Years
United States

Research Site
New Orleans, Louisiana, United States

Miriam Bornhorst, MD, Principal Investigator

NCT Number
Neurofibromatosis type1,
Plexiform Neurofibromas
inoperable, progressive/symptomatic plexiform neurofibromas (PN) without any alternative therapeutic options
mutation in the NF1 gene
Early Access
Intermediate Access Protocol
MeSH Terms
Neurofibromatosis 1
Neurofibroma, Plexiform