Clinical Trials /

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

NCT02129647

Description:

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).

Related Conditions:
  • Schwannoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Axitinib in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas
  • Official Title: Phase II Study of Axitinib in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas

Clinical Trial IDs

  • ORG STUDY ID: 14-00004
  • NCT ID: NCT02129647

Conditions

  • Neurofibromatosis Type 2
  • Vestibular Schwannomas

Interventions

DrugSynonymsArms
AxitinibInlytaAxitinib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
AxitinibExperimental5 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.
  • Axitinib

Eligibility Criteria

        Inclusion criteria

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To estimate the objective volumetric response rates to axitinib in pediatric and adult NF2 patients with VS.
Time Frame:Baseline
Safety Issue:
Description:MRIs at baseline

Secondary Outcome Measures

Measure:To assess the toxicity of axitinib given daily in patients with NF2
Time Frame:Baseline through 1 Year
Safety Issue:
Description:Number of Participants With Treatment-Related Adverse Events as Assessed by neurological examination
Measure:To assess the toxicity of axitinib given daily in patients with NF2
Time Frame:Baseline through 1 Year
Safety Issue:
Description:Number of Participants With Treatment-Related Adverse Events as Assessed by standard laboratory evaluations.
Measure:SF-36
Time Frame:Baseline
Safety Issue:
Description:The SF-36 is a generic measure of QOL and consists of eight domains: physical functioning; role-physical; role-emotional; social functioning; mental health; energy/vitality; bodily pain, and health perception. Scores in each section are normalized to a scale of 0 to 100 (0 = worst possible health state, 100 = best possible health state)
Measure:SF-36
Time Frame:6 Months
Safety Issue:
Description:The SF-36 is a generic measure of QOL and consists of eight domains: physical functioning; role-physical; role-emotional; social functioning; mental health; energy/vitality; bodily pain, and health perception. Scores in each section are normalized to a scale of 0 to 100 (0 = worst possible health state, 100 = best possible health state)
Measure:SF-36
Time Frame:1 Year
Safety Issue:
Description:The SF-36 is a generic measure of QOL and consists of eight domains: physical functioning; role-physical; role-emotional; social functioning; mental health; energy/vitality; bodily pain, and health perception. Scores in each section are normalized to a scale of 0 to 100 (0 = worst possible health state, 100 = best possible health state)
Measure:EURQOL
Time Frame:Baseline
Safety Issue:
Description:Consists of two parts: a descriptive system (Part I) and a visual analogue scale (VAS) (Part II). Part I of the scale consists of 5 single-item dimensions including: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has a 3 point response scale designed to indicate the level of the problem. Part II uses a vertical graduated VAS (thermometer) to measure health status, ranging from worst imaginable health state to best imaginable health state.
Measure:EURQOL
Time Frame:6 Months
Safety Issue:
Description:Consists of two parts: a descriptive system (Part I) and a visual analogue scale (VAS) (Part II). Part I of the scale consists of 5 single-item dimensions including: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has a 3 point response scale designed to indicate the level of the problem. Part II uses a vertical graduated VAS (thermometer) to measure health status, ranging from worst imaginable health state to best imaginable health state.
Measure:EURQOL
Time Frame:1 Year
Safety Issue:
Description:Consists of two parts: a descriptive system (Part I) and a visual analogue scale (VAS) (Part II). Part I of the scale consists of 5 single-item dimensions including: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has a 3 point response scale designed to indicate the level of the problem. Part II uses a vertical graduated VAS (thermometer) to measure health status, ranging from worst imaginable health state to best imaginable health state.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:NYU Langone Health

Trial Keywords

  • Neurofibromatosis Type 2
  • Vestibular Schwannomas
  • Axitinib

Last Updated

May 25, 2021