Phase II Study of Everolimus (RAD001) in Children and Adults With Neurofibromatosis Type 2
Everolimus (RAD001) has been in clinical development since 1996 as an immunosuppressant in
solid organ transplantation and has obtained marketing authorization (Certican®) for
prophylaxis of rejection in renal and cardiac transplantation in a number of countries,
including the majority of the European Union. Everolimus has been in development for
patients with various malignancies since 2002. Everolimus 2.5mg, 5mg and 10mg tablets were
approved under the trade name Afinitor® for patients with advanced renal cell carcinoma
(RCC) after failure of treatment with Sutent® (sunitinib) or Nexavar® (sorafenib) in the US,
EU and several other countries and is undergoing registration in other regions worldwide.
Afinitor® was also recently approved for the treatment of patients with subependymal giant
cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapeutic
intervention but are not candidates for curative surgical resection. Everolimus is being
investigated as an anticancer agent based on its potential to act: 1. Directly on the tumor
cells by inhibiting tumor cell growth and proliferation; and 2. Indirectly by inhibiting
angiogenesis leading to reduced tumor vascularity.
For pediatric cancer patients, safety of RAD001 has been established in a phase 1 trial and
the recommended phase II dose is 5 mg/m2 once daily. This existing pediatric data allows for
inclusion of children in this phase 2 trial, which is an important consideration since some
NF2 patients with the most aggressive clinical course present at school age.
RAD001 was recently approved by the Food and Drug Administration (FDA) for the treatment of
children and adults with subependymal giant cell astrocytoma (SEGA), a benign brain tumor
associated with tuberous sclerosis (TS). Although surgical resection is effective at tumor
reduction, serious complications may follow a radical resection, such as permanent deafness
and facial nerve damage. Most importantly, the tumors often recur after surgery. Radiation
therapy (RT) has been proposed as an alternative. However, its safety and efficacy in the
NF2 population has not been established. A medical therapy option is desperately needed.
This study is a single-center, 2-stage, phase II open-label study. All subjects will get
RAD001 taken continuously until disease progression or unacceptable toxicity. The primary
objective of this study is to look at the objective response rate to RAD001 in patients with
NF2-related tumors including cranial nerve schwannomas, meningiomas and ependymomas.
Participation will consist of screening/baseline visit(s), Day 1, Weeks 1, 2, and 4; and up
to 12 cycles and will include standard of care procedures such as medical history, vital
signs, physical examinations, ECGs, MRIs, audiograms, and laboratory tests. Novartis will
provide the RAD001 free of charge to eligible study subjects. The primary efficacy response
for study purposes will be a greater than or equal to 15% reduction in tumor volume in any
of the target tumors (partial response). Complete disappearance of any of the target tumors
will constitute a complete response (CR).
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To estimate the objective response rates to RAD001 in patients with NF2-related tumors including cranial nerve schwannomas, meningiomas and ependymomas. Radiographic response for study purposes = greater than or equal to 15% reduction in tumor volume in any of the target tumors (partial response). Complete disappearance of any of the target tumors = complete response. MRI of the brain and spine will be performed every 3 months. If an objective response (15% reduction in tumor volume compared to baseline) is observed in any target tumor or stable disease, drug will be continued.
Any point within 12 months from beginning of therapy
Matthias A Karajannis, MD, MS
New York University
United States: Institutional Review Board
RAD001 NF2 (11-00587)
|New York University Medical Center||New York, New York 10016|