A Study of Nilotinib in Growing Vestibular Schwannomas

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by University Health Network, Toronto.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Novartis
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01201538
First received: September 13, 2010
Last updated: June 9, 2011
Last verified: June 2011
  Purpose

Acoustic Neuromas (otherwise known as Vestibular Schwannoma -VS) are benign tumors which grow on the hearing nerve and can cause progressive hearing loss and compression of vital brain structures and even death if it continues. The primary objective of this study is to evaluate the efficacy of Nilotinib in the treatment of patients with progressing VS. Secondary objectives of this study is to evaluate the toxicity profile, quality of life and symptom management of Nilotinib in the treatment of patients with progressing VS.


Condition Intervention Phase
Volumetric Tumor Response and Lack of Tumor Progression
Quality of Life of Patients on Nilotinib Versus Not
Drug: Nilotinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Nilotinib in Growing Vestibular Schwannomas

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • volume change of Vestibular Schwannoma [ Time Frame: 3 years - 1 year drug treatment, 2 year follow-up ] [ Designated as safety issue: Yes ]
    Primary Outcomes of interest will be volumetric tumor response and lack of tumor progression. A response to treatment will be defined as a 20% or greater, change in volume, as defined by Plotkin et al.


Estimated Enrollment: 90
Study Start Date: October 2010
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Nilotinib
    Nilotinib (400 mg bid po) given for 1 year
    Other Name: product name: AMN107 hydrochloride, monohydrate
Detailed Description:

UHN laboratory has demonstrated that targets of Imatinib (c-Kit and PDGFR-α and PDGFR-ß) are overexpressed and activated in both sporadic and NF2 VS.It has also been shown pre-clinically that Imatinib induced a reduction in proliferation and cell viability, with increased apoptosis, in HEI-193 human NF2-null VS cells.Nilotinib is a newer generation RTK inhibitor, with a similar target profile as Imatinib. It was designed by modifying the Imatinib molecule62, and has 30-fold increased potency compared to IImatinib43. In clinical studies of patients with CML or GIST resistant to Imatinib, Nilotinib has demonstrated efficacy with minimal toxicity. Nilotinib (Tasigna®, code number AMN107) was first approved in 2007 for use in Philadelphia chromosome positive CML in the chronic or accelerated phase in patients resistant or intolerant to prior therapy. Thus making Nilotinib an ideal drug to study in understanding its benefit in VS patients.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion

  1. Age >18 years of age with either sporadic or NF-2 associated VS
  2. Growing VS defined as an increase in MRI volumetric growth (minimal 15%) on two successive scans within 18 months prior to registration
  3. Patients may be either treatment naïve or have recurrent VS after previous surgery/ stereotactic radiosurgery
  4. Essentially neurologically asymptomatic (with the exception of sensorineural hearing loss, mild tinnitus and facial numbness) as assessed by the investigator
  5. Karnofsky performance score >70
  6. Adequate renal, haematological, liver function within 7 days prior to registration
  7. Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions
  8. Willingness and ability to provide informed consent

Exclusion

  1. Brain stem compression with symptoms
  2. Symptomatic hydrocephalus
  3. T2/Flair signal changes with distortion of adjacent brain stem and IVth ventricle
  4. Lower cranial nerve dysfunction
  5. Concurrent or previous invasive malignancy, except adequately treated non-melanoma skin cancer or other solid tumours curatively treated with no evidence of disease for ≥ 3 years
  6. Evidence of severe or uncontrolled systemic disease which in the opinion of the investigator makes it undesirable for the subject to participate in the study
  7. Known hypersensitivity to the study drug or drug of similar chemical or biological composition
  8. Impaired cardiac function including

    1. Congenital long QT syndrome or family history of long QT syndrome
    2. Clinically significant resting bradycardia (< 50 beats per minute)
    3. Myocardial infarction within 1 year prior to registration or other clinically significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
    4. History of or current clinically significant ventricular or atrial tachyarrhythmia
    5. QTcF > 450 msec on screening ECG. If QTcF > 450 msec and electrolytes are not within normal ranges then electrolytes should be corrected and the patient rescreened for QTcF.
    6. Unable to monitor the QT/QTc interval on ECG
  9. Treatment with strong CYP3A4 inhibitors or CYP3A4 inducers and treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
  10. Treatment with any medications that have the potential to prolong the QT interval and cannot be either discontinued or switched to a different medication prior to starting study drug.
  11. Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
  12. History of acute or pancreatic disease within one year of study registration or past medical history of chronic pancreatitis.
  13. Acute liver disease
  14. History of significant congenital or acquired bleeding disorder
  15. Use of any investigational agent within 28 days prior to enrollment in the study or foreseen use of an investigational agent during the study
  16. Women who are pregnant or breastfeeding or of childbearing potential without a negative serum pregnancy test within 7 days prior to registration. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male or female patients of childbearing potential unwilling to use effective barrier contraceptives or medical contraceptive to avoid pregnancy throughout the trial and for 3 months following discontinuation.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01201538

Contacts
Contact: Abhijit Guha 416-603-5740 abhijit.guha@uhn.on.ca
Contact: Takyee Tung, B.Sc 416-603-5800 ext 5578

Locations
Canada, Ontario
Toronto Western Hospital Not yet recruiting
Toronto, Ontario, Canada, m5t 2s8
Contact: Abhijit Guha    416-603-5740    abhijit.guha@uhn.on.ca   
Contact: Takyee Tung    416-603-5800 ext 5578    ttung@uhnres.utoronto.ca   
Principal Investigator: Abhijit Guha         
Sub-Investigator: Kim Edelstein         
Sub-Investigator: Normand Laperriere         
Sub-Investigator: Gelareh Zadeh         
Sub-Investigator: Walter Kucharczyk         
Sub-Investigator: John Rutka         
University Health Network Recruiting
Toronto, Ontario, Canada, m5t 2s8
Contact: Abhijit Guha    416-603-5740    abhijit.guha@uhn.on.ca   
Sponsors and Collaborators
University Health Network, Toronto
Novartis
Investigators
Principal Investigator: Abhijit Guha University Health Network, Toronto
  More Information

No publications provided

Responsible Party: Dr. Abhijit Guha, University Health Network
ClinicalTrials.gov Identifier: NCT01201538     History of Changes
Other Study ID Numbers: OZM-024
Study First Received: September 13, 2010
Last Updated: June 9, 2011
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Neurilemmoma
Neuroma, Acoustic
Neoplastic Processes
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neuroma
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Neoplasms by Site
Cranial Nerve Neoplasms
Vestibulocochlear Nerve Diseases
Retrocochlear Diseases
Ear Diseases
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Cranial Nerve Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 20, 2014