Use of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas (NFitor)
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.
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.
- 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.
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.
Neurofibromatosis Type 1
Drug: RAD001: Everolimus
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Single Arm, Multicenter Phase II a Trial of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas That Cannot be Removed by Surgery|
- Radiographic response assessed by MRI analysis [ Time Frame: after 1 year of treatment ] [ Designated as safety issue: No ]
- Radiographic response assessed by MRI analysis [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
- Pain [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
- Deficiency [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
- Quality of life [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
- adverse events [ Time Frame: At 2 years ] [ Designated as safety issue: Yes ]
- laboratory evaluations [ Time Frame: At 2 years ] [ Designated as safety issue: Yes ]
- measurement of vital signs [ Time Frame: At 2 years ] [ Designated as safety issue: Yes ]
- performance of physical examinations [ Time Frame: At 2 years ] [ Designated as safety issue: Yes ]
- all concomitant medications and therapies [ Time Frame: At 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Drug: RAD001: Everolimus
10 mg of RAD001 will be self-administered orally once daily continuously for one year or until unacceptable toxicity or discontinuation from the study from any other reason.
Other Name: RAD001: Everolimus
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01412892
|Henri Mondor Hospital|
|Creteil, France, 94010|
|Principal Investigator:||Pierre Wolkenstein, MD, PhD||Assistance Publique - Hôpitaux de Paris|