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

NCT00973739 | Completed Phase 2 Results DMC

• 1 other identifier: 09-0328
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Neurofibromatosis 2; Vestibular Schwannoma

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

Outcome Measures

Primary Outcomes (1)

• Estimated Volumetric Progression Free Survival at 12 Months

  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 volumetric 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.

  Every three months for one year

Secondary Outcomes (3)

• Estimated Volumetric Progression Free Survival for Hearing at 12 Months

  Every three months for one year

• Participants Experiencing Grades 1 or 2 Toxicities (CTCAE)

  Baseline through one year

• Participants Experiencing Grade 3 Toxicities (CTCAE)

  Baseline through one year

Study Arms (1)

Lapatinib

EXPERIMENTAL

Lapatinib PO dosed according to age: Children/adolescents (less than 18 years of age): 1,800 mg/m2/day PO divided into twice daily doses, to a maximum of 750 mg PO twice daily Adults (18 years of age or older): 1,500 mg PO once daily 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.

Drug: Lapatinib

Interventions

Lapatinib DRUG

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.

Also known as: Tykerb

Lapatinib

Eligibility Criteria

• Age: 4 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be at least 4 years of age.
• 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.
• Significant hearing loss criteria for enrollment.
• Karnofsky (PS) OR Lansky 50-100% (\>16 years of age)
• Absolute neutrophil count ≥ 1,000/mm3 g/dL
• Hemoglobin ≥ 8 g/dL
• Creatinine ≤ 1.5 times upper limit of normal (ULN) OR corrected glomerular filtration rate ≥ 70 ml/min
• Bilirubin ≤ 1.5 times ULN
• ALT ≤ 2.5 times ULN
• Fully recovered from acute toxic effects of any prior chemotherapy, biological modifiers or radiotherapy.
• Steroids are allowed for progressive symptoms but patient must be on a stable dose for at least 1 week prior to study entry.
• Any neurologic deficits must be stable for ≥ 1 week.
• 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.
• Normal cardiac left ventricular ejection fraction (LVEF) by transthoracic echocardiogram.
• Able to provide written informed consent (or consent by parent/legal guardian for minors)

You may not qualify if:

• Patients with serious concurrent infection or medical illness.
• Neurological deficits that are rapidly progressing.
• Patients who are pregnant or breast-feeding.
• Anti-tumor therapy within 4 weeks prior to enrollment.
• Radiation therapy within 2 months prior to enrollment.
• Prior therapy with agents targeting EGFR or ErbB2.
• Any surgery within 4 weeks prior to enrollment.
• Significant gastrointestinal disorder(s)
• Known cardiac disease
• 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.
• 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)

Sponsors & Collaborators

• NYU Langone Health: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

New York University School of Medicine

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Neurofibromatosis 2; Neuroma, Acoustic; Neurilemmoma

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neuroma; Neoplastic Syndromes, Hereditary; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nervous System Neoplasms; Neoplasms by Site; Peripheral Nervous System Neoplasms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Matthias Karajannis, MD
• Organization: New York University Langone Medical Center

matthias.karajannis@nyumc.org

212-263-8400

Study Officials

• Matthias A Karajannis, MD, MS

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2009
• First Posted: September 9, 2009
• Study Start: September 1, 2009
• Primary Completion: October 1, 2012
• Study Completion: November 1, 2012
• Last Updated: March 22, 2016
• Results First Posted: March 22, 2016

Record last verified: 2016-02

Locations

US (1)