Use of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas
Status:
Completed
Trial end date:
2014-10-01
Target enrollment:
Participant gender:
Summary
Background:
Patients with the genetic disorder neurofibromatosis Type 1 (NF1) are at increased risk of
developing tumors of the central and peripheral nervous system. These include plexiform
neurofibromas. The conventional treatment of these internal plexiform neurofibromas is
surgery. This surgery can be possible on a single and limited tumor. On the other hand these
tumors are often surgically intractable due to their multiplicity and their infiltrating
characteristics Increased activity of mammalian target of rapamycin(mTOR) protein is seen in
neurofibromas. mTOR inhibitor rapamycin , or its derivatives such as everolimus may slow or
stop tumor growth in patients with NF1.
Objectives:
Primary objectives To determine whether everolimus has an effect on the volume of surgically
intractable and life-threatening internal plexiform neurofibromas in patients with
neurofibromatosis 1.
Secondary objectives To determine whether everolimus has an effect on the number and the
volume of cutaneous neurofibromas; to determine whether everolimus modify the signaling
pathways in cutaneous neurofibromas.
Eligibility:
- Adults with neurofibromatosis type 1 with at least one internal plexiform neurofibroma,
life-threatening or causing significant morbidity through compression of organs. This or
these internal plexiform neurofibroma(s) should be intractable by surgery.
Design:
An open-label, single arm, non-randomized, single stage phase IIa study. Baseline phase:
Baseline evaluations will be performed within 2 weeks, and up to a maximum of 4 weeks for
specific exams, before the first dose of study drug.
Treatment phase/duration of treatment: All patients will be treated with RAD001 10 mg p.o
daily dose for one year except in case of unacceptable toxicity, death, or discontinuation
from the study for any other reason.
Follow-up phase: All patients will have two follow-up visits scheduled at 18 and 24 months
after the first dose of the study drug to follow for adverse events (AEs) and serious adverse
events (SAEs) that may have occurred after discontinuation from the study and for internal
plexiform neurofibromas assessment.
Radiological review: All Magnetic Resonance Imaging (MRIs) obtained at baseline, during the
treatment period and the follow-up period will be reviewed by the Neuroradiologist of the
study.