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A Phase II Study of Nilotinib in Growing Vestibular Schwannomas

Phase 2
18 Years
Open (Enrolling)
Volumetric Tumor Response and Lack of Tumor Progression, Quality of Life of Patients on Nilotinib Versus Not

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Trial Information

A Phase II Study of Nilotinib in Growing Vestibular Schwannomas

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.

Inclusion Criteria


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


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

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

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

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.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

volume change of Vestibular Schwannoma

Outcome 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.

Outcome Time Frame:

3 years - 1 year drug treatment, 2 year follow-up

Safety Issue:


Principal Investigator

Abhijit Guha

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network, Toronto


Canada: Health Canada

Study ID:




Start Date:

October 2010

Completion Date:

October 2013

Related Keywords:

  • Volumetric Tumor Response and Lack of Tumor Progression
  • Quality of Life of Patients on Nilotinib Versus Not
  • Neurilemmoma
  • Neuroma, Acoustic
  • Neoplastic Processes