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
Intervention: Lapatinib
Intervention description: 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.
Intervention MeSH terms: Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 4 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
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

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must be at least 4 years of age.

          2. Patients must meet diagnostic criteria for NF2 and at least one volumetrically
             measured NF2-related brain or spinal tumor with radiographic evidence of progression
             over the past 12 months, designated as the primary target OR volumetrically measurable
             VS with ipsilateral progressive hearing loss over the past 12 months, designated as
             the primary target tumor.

          3. Significant hearing loss criteria for enrollment.

          4. Karnofsky (PS) OR Lansky 50-100% (>16 years of age)

          5. Absolute neutrophil count ≥ 1,000/mm3 g/dL

          6. Hemoglobin ≥ 8 g/dL

          7. Creatinine ≤ 1.5 times upper limit of normal (ULN) OR corrected glomerular filtration
             rate ≥ 70 ml/min

          8. Bilirubin ≤ 1.5 times ULN

          9. ALT ≤ 2.5 times ULN

         10. Fully recovered from acute toxic effects of any prior chemotherapy, biological
             modifiers or radiotherapy.

         11. Steroids are allowed for progressive symptoms but patient must be on a stable dose for
             at least 1 week prior to study entry.

         12. Any neurologic deficits must be stable for ≥ 1 week.

         13. Patients with the potential for pregnancy or impregnating their partner must agree to
             follow acceptable birth control methods to avoid conception. Women of childbearing
             potential must have a negative pregnancy test. The anti-proliferative activity of this
             experimental drug may be harmful to the developing fetus.

         14. Normal cardiac left ventricular ejection fraction (LVEF) by transthoracic
             echocardiogram.

         15. Able to provide written informed consent (or consent by parent/legal guardian for
             minors)

        Exclusion Criteria:

          1. Patients with serious concurrent infection or medical illness.

          2. Neurological deficits that are rapidly progressing.

          3. Patients who are pregnant or breast-feeding.

          4. Anti-tumor therapy within 4 weeks prior to enrollment.

          5. Radiation therapy within 2 months prior to enrollment.

          6. Prior therapy with agents targeting EGFR or ErbB2.

          7. Any surgery within 4 weeks prior to enrollment.

          8. Significant gastrointestinal disorder(s)

          9. Known cardiac disease

         10. Patients with a concurrent or prior malignancy are ineligible unless they are patients
             with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin.
             Patients who have been free of disease (any prior malignancy) for more than five years
             are eligible for this study.

         11. Patients cannot have received cytochrome P450-inducing anticonvulsants (EIADs; e.g.,
             phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) or similar agents
             (e.g., rifampin) or P450-inhibiting agents (Ketoconazole, Itraconazole,
             Clarithromycin, Atazanavir, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir,
             Telithromycin, Voriconazole)