Study of Axitinib in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas

NCT02129647 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 14-00004
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Neurofibromatosis Type 2; Vestibular Schwannomas

Keywords

Neurofibromatosis Type 2; Vestibular Schwannomas; Axitinib

Outcome Measures

Primary Outcomes (5)

• 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).

  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).

  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).

  10 days

• Pre-Operative Everolimus Blood Levels

  Baseline

• Post-Operative Everolimus Blood Levels

  10 days

Study Arms (1)

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.

Drug: Axitinib

Interventions

Axitinib DRUG

Also known as: Inlyta

Axitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Medical Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Neurofibromatosis 2; Neuroma, Acoustic

Interventions

Axitinib

Condition Hierarchy (Ancestors)

Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neuroma; Neoplastic Syndromes, Hereditary; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nervous System Neoplasms; Neoplasms by Site; Peripheral Nervous System Neoplasms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Theodore Nicolaides
• Organization: NYU Langone

Theodore.Nicolaides@nyualangone.org

212-263-9959

Study Officials

• Theodore Nicolaides, MD

  NYU Langone Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2014
• First Posted: May 2, 2014
• Study Start: April 1, 2014
• Primary Completion: February 5, 2019
• Study Completion: February 5, 2019
• Last Updated: December 1, 2021
• Results First Posted: December 1, 2021

Record last verified: 2021-11

Locations

US (1)