Growing Vestibular SchwannomasPhase 2NCT01201538
A Study of Nilotinib in Growing Vestibular Schwannomas
A Phase 2 study testing Nilotinib in people with Growing Vestibular Schwannomas, run by University Health Network, Toronto at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Growing Vestibular Schwannomas
- What is being tested?
- Nilotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesCanada
- Study dates
- Oct 2010to Oct 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Toronto Western Hospital
Toronto, Ontario, m5t 2s8
University Health Network
Toronto, Ontario, m5t 2s8
About this study
Official title: A Phase II Study of Nilotinib in Growing Vestibular Schwannomas
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.
Read the 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.
- Conditions
- Growing Vestibular Schwannomas
- Being tested
- Nilotinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Not described Receives: Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years - 1 year drug treatment, 2 year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2010 (estimated)
- Study startOct 2010
- Primary completionOct 2011
- Study completionOct 2013
Why it stopped: Study PI passed away We had trouble recruiting for the drug arm
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Growing Vestibular SchwannomasStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Abhijit Guha, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01201538
- Sponsor's protocol ID
- OZM-024
- Status last verified
- Jan 2017
- First submitted
- 13 Sep 2010
- Last updated
- 11 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Nilotinib in Growing Vestibular Schwannomas
- ClinicalTrials.gov ID
- NCT01201538
- Acronym / sponsor ID
- OZM-024
- Conditions
- Growing Vestibular Schwannomas
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study PI passed away We had trouble recruiting for the drug arm
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Oct 2010
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 14 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: Nilotinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nilotinib | Drug | Single arm |
Primary outcome
volume change of Vestibular Schwannoma
Time frame: 3 years - 1 year drug treatment, 2 year follow-up
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.
Results and safety
The study was stopped early (reason given: Study PI passed away We had trouble recruiting for the drug arm). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2017.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abhijit Guha principal investigator
University Health Network, Toronto
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nilotinib in people with Growing Vestibular Schwannomas, run by University Health Network, Toronto at 2 sites in Canada.
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 8 inclusion and 22 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: stopped early, as of the sponsor's last update on 11 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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?
The study was stopped early (reason given: Study PI passed away We had trouble recruiting for the drug arm). Results are not available in the source record.
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?
volume change of Vestibular Schwannoma (time frame: 3 years - 1 year drug treatment, 2 year follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jan 2017.