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

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

Official Title: Phase II Study of Lapatinib in Children and Adults With Neurofibromatosis Type 2(NF2) and NF2-related Tumors

Brief 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 Summary:

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.

Sponsor: New York University School of Medicine

Current Primary Outcome: Estimated Volumetric Progression Free Survival at 12 Months [ Time Frame: Every three months for one year ]

Original Primary Outcome: 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 ]

Current Secondary Outcome:

• Estimated Volumetric Progression Free Survival for Hearing at 12 Months [ Time Frame: Every three months for one year ]

  Measurements were taken every three months, up to one year. Estimated volumetric progression free survival (PFS) was measured from date of enrollment to date of hearing progression. PFS was analyzed using the Kaplan-Meier method in terms of overall PFS (volumetric or hearing progression), volumetric progression, and hearing progression.

  Point estimates for PFS with 95% confidence intervals (CIs) were calculated from Kaplan-Meier curves.

• Participants Experiencing Grades 1 or 2 Toxicities (CTCAE) [ Time Frame: Baseline through one year ]
  Toxicity was assessed throughout the study, up to one year.
• Participants Experiencing Grade 3 Toxicities (CTCAE) [ Time Frame: Baseline through one year ]
  Toxicity was assessed throughout the study, up to one year.

Original Secondary Outcome:

• To assess the toxicity of Lapatinib given daily in patients with NF2. [ Time Frame: Monthly for one year ]
• 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 ]

Information By: New York University School of Medicine

Dates:
Date Received: September 3, 2009
Date Started: September 2009
Date Completion:
Last Updated: February 19, 2016
Last Verified: February 2016