Clinical Trial: Use of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 we

Detailed Summary:

Neurofibromatosis 1 (NF1) is an autosomal dominant disease affecting 1 in 3000 to 1 in 4000 people. NF1 is characterized by multiple dermal neurofibromas, plexiform neurofibromas, malignant peripheral nerve sheath tumors (MPNST), and optic pathway gliomas, as well as by café-au-lait spots and abnormalities of the skeletal, cardiovascular and central nervous systems. The NF1 gene is located on chromosome 17q11.2, and its protein, neurofibromin, functions as a tumor suppressor.

People with NF1 have a decrease in life expectancy of 15 years, with MPNST as a leading cause of death in young adults. A specific phenotype at risk of mortality has been identified, patients with subcutaneous neurofibromas. Individuals with subcutaneous neurofibromas are more than 3 times as likely to have internal plexiform neurofibromas as others. Individuals with internal plexiform neurofibromas are 18 times more likely to develop MPNST than patients without internal plexiform neurofibromas. Beside MPNST, internal plexiform neurofibromas can be life-threatening or cause of significant morbidity through compression of organs mainly spine or nerve roots.

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. In this context a medical treatment decreasing the size of these tumors would have its place with as short term aim to lower the consequence of compression and long-term aim to reduce the risk of malignant transformation.

NF1 is a consequence of the loss-of-function mutations in the NF1 tumor suppressor gene. The NF1-encoded protein, neurofibromin, functions as a Ras-GTPase activ
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Radiographic response assessed by MRI analysis [ Time Frame: after 1 year of treatment ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Radiographic response assessed by MRI analysis [ Time Frame: At 2 years ]
  • Overall survival [ Time Frame: At 2 years ]
  • Pain [ Time Frame: At 2 years ]
  • Deficiency [ Time Frame: At 2 years ]
  • Quality of life [ Time Frame: At 2 years ]
  • adverse events [ Time Frame: At 2 years ]
  • laboratory evaluations [ Time Frame: At 2 years ]
  • measurement of vital signs [ Time Frame: At 2 years ]
  • performance of physical examinations [ Time Frame: At 2 years ]
  • all concomitant medications and therapies [ Time Frame: At 2 years ]


Original Secondary Outcome: Same as current

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: August 8, 2011
Date Started: April 2011
Date Completion:
Last Updated: November 13, 2014
Last Verified: November 2014