Lapatinib Study for Children and Adults With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors
Condition: Neurofibromatosis 2; Vestibular Schwannoma
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurilemmoma; Neuroma, Acoustic; Neurofibromatosis 2
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine if Lapatinib has any effect on tumors found in
      patients with Neurofibromatosis Type 2 (NF2). NF2 is a condition that mainly affects the skin
      and nervous system. It causes non-cancerous tumors (which are known as neuromas) to grow on
      the nerves around a person's body. Some signs of NF2 include a gradual loss of hearing and
      tumors growing on the skin, the brain and the spinal cord which can lead to complications.

      Lapatinib is an oral drug that is approved by Food and Drug Administration (FDA) for other
      types of tumors, it is not approved by the FDA for treatment of NF2 related tumors. The
      investigators know a lot about how well it is tolerated, but the investigators do not know if
      it is effective in treating your condition, therefore it is considered to be an
      investigational medication. This study will test whether Lapatinib may shrink tumors commonly
      found in patients with NF2 or stop them from growing. This will help us to decide if
      Lapatinib should be used to treat NF2 patients in future. Lapatinib is a drug that has been
      used for over 10 years to treat various forms of cancer. It has not been studied for the
      treatment of tumors in NF2 patients.
    

Detailed description: 
      In this trial, we propose to assess the objective response rates to Lapatinib in patients
      with NF2-related tumors. Lapatinib is a commercially available inhibitor of ErbB2 and EGF.
      Data suggests that abnormal signaling via EGFR and ErbB2 is a major contributor to tumor
      growth and progression in both sporadic and NF2-related VS and that inhibition of this
      signaling pathway can result in decreased tumor growth.

      Demonstrating that Lapatinib produces an objective response to reduce tumor volume or
      stabilize disease will provide additional treatment options for NF patients with multiple
      tumor growth. For patients with VS we expect to see ≥ 10 dB improvement in PTA and/or
      improvement in SDS, compared to the audiogram at initiation of treatment. Currently there are
      no available treatment options for NF2 patients with multiple tumors. Depending on tumor cell
      type, lapatinib has cytostatic or cytotoxic antitumor effects, and in a recent study
      assessing the biological effects of Lapatinib on the associated molecular pathways and tumor
      growth in patients with solid tumors, a correlation was seen between tumor response and
      pre-treatment levels of (phosphor)-ErbB2 and (phosphor)-ERK1/2.
    

Intervention name(s): Lapatinib
Intervention type(s): Drug
Intervention description(s): Lapatinib is dosed according to age. Lapatinib is available in 250 mg tablets only. For pediatric dosing, the total daily dose will be rounded up or down to the nearest 250 mg increment.
Children/adolescents (<18 years of age): 1,800 mg/m2/day PO divided into twice daily doses, to a maximum of 750 mg PO (3 tablets twice daily)
Adults (>=18 years of age): 1,500 mg PO (6 tablets once daily)
Duration: Up to 12 months, depending on treatment response.
Other intervention name(s): Tykerb
Intervention MeSH terms: Lapatinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: NF-2; NF-2 related tumors; Schwannoma, Acoustic, Bilateral; schwannomas; Neurilemmoma of other cranial and peripheral nerves; NF2 related benign intracranial tumors including; NF2 related meningiomas; NF2 related ependymomas; NF2 related spinal neurofibromas; NF2 related gliomas