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
Approximately 100 patients in the US will be treated as part of this protocol
Brief Title
An Intermediate Access Protocol for Selumetinib for Treatment of Neurofibromatosis Type 1
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
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
Categories
Conditions
NF type1 With Inoperable Plexiform Neurofibromas
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 transplant
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
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 transplant
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
Inclusion 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.
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.
Gender
All
Gender Based
false
Keywords
Neurofibromatosis type1,
Plexiform Neurofibromas
inoperable, progressive/symptomatic plexiform neurofibromas (PN) without any alternative therapeutic options
mutation in the NF1 gene
Selumetinib
Early Access
Intermediate Access Protocol
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
130 Years
Minimum Age
2 Years
NCT Id
NCT03259633
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D1346R00002
Overall Status
Approved for marketing
Official Title
An Intermediate Access Protocol for Selumetinib for Treatment of Neurofibromatosis Type 1 With Inoperable, Progressive/Symptomatic Plexiform Neurofibromas (PN)
Secondary Ids
Secondary Id
D1346R00002
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
130
Minimum Age Number (converted to Years and rounded down)
2
Investigators
Investigator Type
Principal Investigator
Investigator Name
Nagma Dalvi
Investigator Email
ndalvi@montefiore.org
Investigator Phone