A Study of Nilotinib in Growing Vestibular Schwannomas
Primary Purpose
Growing Vestibular Schwannomas
Status
Terminated
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Nilotinib
Sponsored by
About this trial
This is an interventional treatment trial for Growing Vestibular Schwannomas
Eligibility Criteria
Inclusion
- Age >18 years of age with either sporadic or NF-2 associated VS
- Growing VS defined as an increase in MRI volumetric growth (minimal 15%) on two successive scans within 18 months prior to registration
- Patients may be either treatment naïve or have recurrent VS after previous surgery/ stereotactic radiosurgery
- Essentially neurologically asymptomatic (with the exception of sensorineural hearing loss, mild tinnitus and facial numbness) as assessed by the investigator
- Karnofsky performance score >70
- Adequate renal, haematological, liver function within 7 days prior to registration
- Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions
- Willingness and ability to provide informed consent
Exclusion
- Brain stem compression with symptoms
- Symptomatic hydrocephalus
- T2/Flair signal changes with distortion of adjacent brain stem and IVth ventricle
- Lower cranial nerve dysfunction
- 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
- 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
- Known hypersensitivity to the study drug or drug of similar chemical or biological composition
Impaired cardiac function including
- Congenital long QT syndrome or family history of long QT syndrome
- Clinically significant resting bradycardia (< 50 beats per minute)
- Myocardial infarction within 1 year prior to registration or other clinically significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
- History of or current clinically significant ventricular or atrial tachyarrhythmia
- 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.
- Unable to monitor the QT/QTc interval on ECG
- 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.
- 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.
- Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
- History of acute or pancreatic disease within one year of study registration or past medical history of chronic pancreatitis.
- Acute liver disease
- History of significant congenital or acquired bleeding disorder
- Use of any investigational agent within 28 days prior to enrollment in the study or foreseen use of an investigational agent during the study
- 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.
Sites / Locations
- Toronto Western Hospital
- University Health Network
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm
Arm Description
Outcomes
Primary Outcome Measures
volume change of Vestibular Schwannoma
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01201538
First Posted
September 13, 2010
Last Updated
January 10, 2017
Sponsor
University Health Network, Toronto
Collaborators
Novartis
1. Study Identification
Unique Protocol Identification Number
NCT01201538
Brief Title
A Study of Nilotinib in Growing Vestibular Schwannomas
Official Title
A Phase II Study of Nilotinib in Growing Vestibular Schwannomas
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Terminated
Why Stopped
Study PI passed away We had trouble recruiting for the drug arm
Study Start Date
October 2010 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
Collaborators
Novartis
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Growing Vestibular Schwannomas
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single arm
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Nilotinib
Primary Outcome Measure Information:
Title
volume change of Vestibular Schwannoma
Description
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.
Time Frame
3 years - 1 year drug treatment, 2 year follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion
Age >18 years of age with either sporadic or NF-2 associated VS
Growing VS defined as an increase in MRI volumetric growth (minimal 15%) on two successive scans within 18 months prior to registration
Patients may be either treatment naïve or have recurrent VS after previous surgery/ stereotactic radiosurgery
Essentially neurologically asymptomatic (with the exception of sensorineural hearing loss, mild tinnitus and facial numbness) as assessed by the investigator
Karnofsky performance score >70
Adequate renal, haematological, liver function within 7 days prior to registration
Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions
Willingness and ability to provide informed consent
Exclusion
Brain stem compression with symptoms
Symptomatic hydrocephalus
T2/Flair signal changes with distortion of adjacent brain stem and IVth ventricle
Lower cranial nerve dysfunction
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
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
Known hypersensitivity to the study drug or drug of similar chemical or biological composition
Impaired cardiac function including
Congenital long QT syndrome or family history of long QT syndrome
Clinically significant resting bradycardia (< 50 beats per minute)
Myocardial infarction within 1 year prior to registration or other clinically significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
History of or current clinically significant ventricular or atrial tachyarrhythmia
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.
Unable to monitor the QT/QTc interval on ECG
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.
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.
Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
History of acute or pancreatic disease within one year of study registration or past medical history of chronic pancreatitis.
Acute liver disease
History of significant congenital or acquired bleeding disorder
Use of any investigational agent within 28 days prior to enrollment in the study or foreseen use of an investigational agent during the study
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abhijit Guha
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Toronto Western Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
m5t 2s8
Country
Canada
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
m5t 2s8
Country
Canada
12. IPD Sharing Statement
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A Study of Nilotinib in Growing Vestibular Schwannomas
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