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

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ClinicalTrials.gov Identifier: NCT00973739
Recruitment Status : Completed
First Posted : September 9, 2009
Results First Posted : March 22, 2016
Last Update Posted : March 22, 2016
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
NYU Langone Health

Tracking Information
First Submitted Date  ICMJE September 3, 2009
First Posted Date  ICMJE September 9, 2009
Results First Submitted Date  ICMJE June 27, 2013
Results First Posted Date  ICMJE March 22, 2016
Last Update Posted Date March 22, 2016
Study Start Date  ICMJE September 2009
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2016)
Estimated Volumetric Progression Free Survival 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 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 8, 2009)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2016)
  • 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 Measures  ICMJE
 (submitted: September 8, 2009)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lapatinib Study for Children and Adults With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors
Official Title  ICMJE 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neurofibromatosis 2
  • Vestibular Schwannoma
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Lapatinib

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.

Intervention: Drug: Lapatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 19, 2016)
21
Original Estimated Enrollment  ICMJE
 (submitted: September 8, 2009)
17
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 80 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00973739
Other Study ID Numbers  ICMJE 09-0328
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NYU Langone Health
Study Sponsor  ICMJE NYU Langone Health
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Principal Investigator: Matthias A Karajannis, MD, MS NYU School of Medicine
PRS Account NYU Langone Health
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP