Lapatinib Study for Children and Adults With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00973739
First received: September 3, 2009
Last updated: October 18, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Neurofibromatosis 2
Vestibular Schwannoma
Drug: Lapatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Lapatinib in Children and Adults With Neurofibromatosis Type 2(NF2) and NF2-related Tumors

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • To estimate the objective response rates to Lapatinib in patients with NF2-related tumors including cranial nerve schwannomas, meningiomas and ependymomas. [ Time Frame: Every three months for one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the toxicity of Lapatinib given daily in patients with NF2. [ Time Frame: Monthly for one year ] [ Designated as safety issue: Yes ]
  • To examine the association of objective measures of response on MRI, i.e. volumetric tumor analysis and perfusion with clinical measures of response, i.e. audiogram in patients with vestibular schwannomas (VS). [ Time Frame: Every three months for one year ] [ Designated as safety issue: No ]

Estimated Enrollment: 17
Study Start Date: September 2009
Estimated Study Completion Date: December 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Lapatinib

    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 Name: Tykerb
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.

  Eligibility

Ages Eligible for Study:   4 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00973739

Locations
United States, New York
New York University School of Medicine
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
GlaxoSmithKline
Investigators
Principal Investigator: Matthias A Karajannis, MD, MS NYU School of Medicine
  More Information

No publications provided

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00973739     History of Changes
Other Study ID Numbers: 09-0328
Study First Received: September 3, 2009
Last Updated: October 18, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
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

Additional relevant MeSH terms:
Neurilemmoma
Neurofibromatoses
Neurofibromatosis 1
Neuroma, Acoustic
Neurofibromatosis 2
Neurofibroma
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neuromuscular Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroma
Cranial Nerve Neoplasms
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Vestibulocochlear Nerve Diseases
Retrocochlear Diseases
Ear Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on October 01, 2014