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Neurofibromatosis 2Phase 2NCT00973739

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

A Phase 2 study testing Lapatinib in people with Neurofibromatosis 2 and Vestibular Schwannoma, run by NYU Langone Health at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 4 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Neurofibromatosis 2, Vestibular Schwannoma
What is being tested?
Lapatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
Sep 2009to Nov 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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.
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • New York University School of Medicine

    New York, New York, 10016

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Lapatinib
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
Medical subject headings
Neurofibromatosis 2, Neuroma, Acoustic, Neurilemmoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LapatinibDrug

    Also called Tykerb

    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.

Study groups in NCT00973739
Study groupRoleWhat they receive
LapatinibExperimentalLapatinib 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.
Receives: Drug: Lapatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Every three months for one year

Secondary outcomes (3)

  1. Estimated Volumetric Progression Free Survival for Hearing 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 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.

    Measured: Every three months for one year

  2. Participants Experiencing Grades 1 or 2 Toxicities (CTCAE)

    Toxicity was assessed throughout the study, up to one year.

    Measured: Baseline through one year

  3. Participants Experiencing Grade 3 Toxicities (CTCAE)

    Toxicity was assessed throughout the study, up to one year.

    Measured: Baseline through one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionOct 2012
  4. Study completionNov 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00973739
Sponsor's protocol ID
09-0328
Status last verified
Feb 2016
First submitted
3 Sep 2009
Last updated
22 Mar 2016
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lapatinib in people with Neurofibromatosis 2 and Vestibular Schwannoma, run by NYU Langone Health at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Estimated Volumetric Progression Free Survival at 12 Months (time frame: Every three months for one year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00973739.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2016.

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