Neurofibromatosis Type 2Phase 2NCT02129647
Study of Axitinib in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas
A Phase 2 study testing Axitinib in people with Neurofibromatosis Type 2 and Vestibular Schwannomas, run by NYU Langone Health at 1 site in United States.
Trial summary
The purpose of this study is to determine if the study drug, AXITINIB, has any effect on tumors found in patients with Neurofibromatosis Type 2 (NF2). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurofibromatosis Type 2, Vestibular Schwannomas
- What is being tested?
- Axitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to 5 Feb 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Meets clinical diagnostic criteria for NF2
- At least one volumetrically measurable and ≥1 cc NF2-related VS (histological confirmation not required)
- MRI evidence of progression (either as >2 mm increase in maximum linear diameter on conventional MRI, or a >20%volume increase by 3D volumetrics) over the past ≤18 months, OR progressive hearing loss, defined as a decline in word recognition score below the 95% critical difference interval from baseline score related to VS (i.e., not due to prior interventions such as surgery or radiation)
- Karnofsky performance status (PS) 60-100%. Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Adequate bone marrow function as shown by: absolute neutrophil count ≥1.5 x 10^9/L, Platelets ≥100 x 10^9/L, Hb >9 g/dL
Show all 35Show fewer
- Adequate liver function as shown by:
- serum bilirubin ≤1.5 x upper limit of normal (ULN)
- ALT and AST ≤2.5x ULN
- INR ≤1.5. (anticoagulation with low molecular weight heparin is allowed if on a stable dose for >2 weeks at time of enrollment.)
- Adequate renal function: serum creatinine ≤1.5 x ULN
- Fully recovered from acute toxic effects of any prior chemotherapy, biological modifiers or radiotherapy
- Any neurologic deficits must be stable for ≥1 week
- Able to provide signed informed consent Exclusion criteria
- Patients currently receiving medical anticancer therapies or who have received medical anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, antibody based therapy, etc.)
- Radiation therapy to a study target tumor within 1 year prior to enrollment, or any radiation therapy within 4 weeks prior to enrollment.
- Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
- Prior treatment with bevacizumab or other agents targeting vascular endothelial growth factor (VEGF) or VEGF receptor
- Prior treatment with any investigational drug within the preceding 4 weeks
- Unstable or rapidly progressive disease, including patients who require glucocorticoids for symptomatic control of brain or spinal tumors
- Treatment with strong CYP3A4 enzyme inhibitors or inducers, including but not limited to ketoconazole, itraconazole, ritonavir, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital and St. John's wort
- Requirement of therapeutic anticoagulant therapy with oral vitamin K antagonists; low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed; therapeutic use of low molecular weight heparin (or similar parenteral drug) for venous-thromboembolic disease is allowed.
- Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic congestive heart failure of New York heart Association Class III or IV
- unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- severely impaired lung function as defined as spirometry and diffusion capacity of lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 90% or less at rest on room air
- active (acute or chronic) or uncontrolled severe infections
- liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of axitinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active bleeding diathesis
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes. (Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to administration of axitinib)
- Male patient whose sexual partner(s) are women of child bearing potential, who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
- History of noncompliance to medical regimens
- Patients unwilling to or unable to comply with the protocol
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
NYU Langone Medical Center
New York, New York, 10016
About this study
Official title: Phase II Study of Axitinib in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas
The purpose of this study is to determine if the study drug, AXITINIB, has any effect on tumors found in patients with Neurofibromatosis Type 2 (NF2).
Read the detailed description
NF2 is a condition that mainly affects the skin and nervous system. It causes non-cancerous tumors 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.
AXITINIB is an oral drug (taken by mouth) that is approved by the United States Food and Drug Administration (FDA) for the treatment of other types of tumors. However, in this research study, AXITINIB is considered investigational because it is not approved by the FDA for treatment of NF2. Much is known regarding how well it is tolerated (handled), but investigators do not know if it is effective in treating NF2.
This research study will test whether AXITINIB may shrink tumors commonly found in patients with NF2 or stop them from growing. This will help to decide if AXITINIB should be used to treat NF2 patients in the future. AXITINIB is a drug that has been used to treat various forms of cancer. It has not been studied for the treatment of tumors in NF2 patients. Investigators have selected AXITINIB for this clinical trial in patients with NF2 and NF2-related tumors because a very similar drug, bevacizumab, can shrink Vestibular Schwannomas (VS) in some NF2 patients.
Pfizer, Inc., the manufacturer of the study drug, AXITINIB, will provide the AXITINIB being used in this study.
Primary Objective: To estimate the objective volumetric response rates to axitinib in adult NF2 patients with VS.
Secondary Objectives: To assess the toxicity of axitinib given daily in patients with NF2 and to examine the association of objective measures of response on MRI, i.e. volumetric tumor analysis with clinical measures of response, i.e. (audiogram), as well as quality of life assessments (NFTI-QOL). In addition, response in non-VS tumors, such as other schwannomas and meningiomas, may be explored.
- Conditions
- Neurofibromatosis Type 2, Vestibular Schwannomas
- Being tested
- Axitinib
- Keywords
- Neurofibromatosis Type 2, Vestibular Schwannomas, Axitinib
- Medical subject headings
- Neurofibromatosis 2, Neuroma, Acoustic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AxitinibDrug
Also called Inlyta
| Study group | Role | What they receive |
|---|---|---|
| Axitinib | Experimental | 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks, respectively, provided no adverse reactions (i.e., not exceeding grade 2 toxicities) and normotensive and not receiving antihypertension medications. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity. Receives: Drug: Axitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Expression Levels of p-S6 Based Immunohistochemistry (Histoscore)
The histoscore is given as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level (0 = none, 1 = weak, 2 = moderate, 3 = strong). With 4 intensity levels, the resulting score ranged from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).
Measured: 10 days
Expression Levels of p-ERK Based Immunohistochemistry (Histoscore)
The histoscore is given as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level (0 = none, 1 = weak, 2 = moderate, 3 = strong). With 4 intensity levels, the resulting score ranged from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).
Measured: 10 days
Expression Levels of p-AKT Based Immunohistochemistry (Histoscore)
The histoscore is given as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level (0 = none, 1 = weak, 2 = moderate, 3 = strong). With 4 intensity levels, the resulting score ranged from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).
Measured: 10 days
Pre-Operative Everolimus Blood Levels
Measured: Baseline
Post-Operative Everolimus Blood Levels
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2014 (estimated)
- Study startApr 2014
- Primary completion5 Feb 2019
- Study completion5 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neurofibromatosis Type 2Studies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Theodore Nicolaides, MD, Principal investigator, NYU Langone Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02129647
- Sponsor's protocol ID
- 14-00004
- Status last verified
- Nov 2021
- First submitted
- 29 Apr 2014
- Last updated
- 1 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Axitinib in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas
- ClinicalTrials.gov ID
- NCT02129647
- Acronym / sponsor ID
- 14-00004
- Conditions
- Neurofibromatosis Type 2, Vestibular Schwannomas
- Keywords
- Neurofibromatosis Type 2, Vestibular Schwannomas, Axitinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- 5 Feb 2019 (actual)
- Study completion
- 5 Feb 2019 (actual)
- First posted
- 2 May 2014 (estimated)
- Results
- Posted 1 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if the study drug, AXITINIB, has any effect on tumors found in patients with Neurofibromatosis Type 2 (NF2).
Detailed description
NF2 is a condition that mainly affects the skin and nervous system. It causes non-cancerous tumors 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.
AXITINIB is an oral drug (taken by mouth) that is approved by the United States Food and Drug Administration (FDA) for the treatment of other types of tumors. However, in this research study, AXITINIB is considered investigational because it is not approved by the FDA for treatment of NF2. Much is known regarding how well it is tolerated (handled), but investigators do not know if it is effective in treating NF2.
This research study will test whether AXITINIB may shrink tumors commonly found in patients with NF2 or stop them from growing. This will help to decide if AXITINIB should be used to treat NF2 patients in the future. AXITINIB is a drug that has been used to treat various forms of cancer. It has not been studied for the treatment of tumors in NF2 patients. Investigators have selected AXITINIB for this clinical trial in patients with NF2 and NF2-related tumors because a very similar drug, bevacizumab, can shrink Vestibular Schwannomas (VS) in some NF2 patients.
Pfizer, Inc., the manufacturer of the study drug, AXITINIB, will provide the AXITINIB being used in this study.
Primary Objective: To estimate the objective volumetric response rates to axitinib in adult NF2 patients with VS.
Secondary Objectives: To assess the toxicity of axitinib given daily in patients with NF2 and to examine the association of objective measures of response on MRI, i.e. volumetric tumor analysis with clinical measures of response, i.e. (audiogram), as well as quality of life assessments (NFTI-QOL). In addition, response in non-VS tumors, such as other schwannomas and meningiomas, may be explored.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Axitinib | Experimental | Drug: Axitinib5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks, respectively, provided no adverse reactions (i.e., not exceeding grade 2 toxicities) and normotensive and not receiving antihypertension medications. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Age ≥18 years
- Meets clinical diagnostic criteria for NF2
- At least one volumetrically measurable and ≥1 cc NF2-related VS (histological confirmation not required)
- MRI evidence of progression (either as >2 mm increase in maximum linear diameter on conventional MRI, or a >20%volume increase by 3D volumetrics) over the past ≤18 months, OR progressive hearing loss, defined as a decline in word recognition score below the 95% critical difference interval from baseline score related to VS (i.e., not due to prior interventions such as surgery or radiation)
- Karnofsky performance status (PS) 60-100%. Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| AxitinibAlso: Inlyta | Drug | Axitinib |
Primary outcome
Expression Levels of p-S6 Based Immunohistochemistry (Histoscore)
Time frame: 10 days
The histoscore is given as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level (0 = none, 1 = weak, 2 = moderate, 3 = strong). With 4 intensity levels, the resulting score ranged from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).
Expression Levels of p-ERK Based Immunohistochemistry (Histoscore)
Time frame: 10 days
The histoscore is given as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level (0 = none, 1 = weak, 2 = moderate, 3 = strong). With 4 intensity levels, the resulting score ranged from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).
Expression Levels of p-AKT Based Immunohistochemistry (Histoscore)
Time frame: 10 days
The histoscore is given as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level (0 = none, 1 = weak, 2 = moderate, 3 = strong). With 4 intensity levels, the resulting score ranged from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).
Pre-Operative Everolimus Blood Levels
Time frame: Baseline
Post-Operative Everolimus Blood Levels
Time frame: 10 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Theodore Nicolaides, MD principal investigator
NYU Langone Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Axitinib in people with Neurofibromatosis Type 2 and Vestibular Schwannomas, run by NYU Langone Health at 1 site in United States.
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 35 inclusion and 0 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: finished, as of the sponsor's last update on 1 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Yes. Results are posted in the registry (first posted 1 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Expression Levels of p-S6 Based Immunohistochemistry (Histoscore) (time frame: 10 days). The study lists 5 primary outcomes in all. 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 1 Dec 2021.