Trial Information

A Prospective Natural History Study of Patients With Neurofibromatosis Type 2 (NF2)

Objective

The objective of this prospective natural history study on neurofibromatosis type 2 (NF2) is
to gain clinical and molecular insight into the effects of this tumor suppressor syndrome on
tumor development and progression and to identify factors linked to symptom evolution.

Study Population

Two hundred fifty patients, ages 8-75, with a clinical or genetic diagnosis of NF2 will
participate in this study.

Design

Study participants will be evaluated with a thorough physical and neurologic examination
upon enrollment. This initial outpatient evaluation will include ophthalmologic
examination, magnetic resonance imaging with contrast of the craniospinal axis, NF2 research
blood procurement and serum biomarker testing. Patients with measurable hearing will have
audiology assessment performed during the initial visit. Patients with untreated vestibular
schwannomas will have vestibular assessment performed during the initial visit.

Patients with tumors that affect speech and swallowing production will be seen by a speech
language pathologist at the following visit, where a standard clinical assessment of speech
and swallowing function will be done. In patients with tumors that affect independent
functioning associated with activities of daily living, a physical therapy and occupational
therapy assessment will be performed at the following visit.

Subjects will be followed as outpatients for five years, during which clinical, radiologic
and serum biomarker evaluation will be performed every six months. Auditory testing will be
performed annually for patients with measurable hearing. Patients with initially untreated
vestibular schwannomas will be followed annually with vestibular testing. Ophthalmologic
evaluation will performed every one to three years, depending on the severity of ocular
lesions. Peri-operative speech and swallowing reassessments will be performed as medically
indicated, when tumors that may affect these abilities are treated. Functional status
testing will be repeated peri-operatively and annually thereafter when tumors that may
affect independent functioning are treated.

If clinical symptoms attributable to any NF2-associated lesion are progressive in nature or
warrant treatment intervention, testing may be repeated more frequently.

Outcome measures

Based on data derived from this study, we hope to identify factors that predict tumor
development, forecast tumor growth and that underlie symptom formation. These findings
should permit the safer treatment of the subset of tumors that will cause symptoms and avoid
the unnecessary treatment of lesions that will remain stable (not requiring treatment) in
these patients. Moreover, this prospective natural history study should be useful in
identifying the stochastic factors that underlie the biology of these tumors.