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:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">Axitinib</span> in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas

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

    NCT ID: NCT02129647

    ORG ID: s14-00004

    Trial Conditions

    Neurofibromatosis Type 2

    Vestibular Schwannomas

    Trial Interventions

    Drug Synonyms Arms
    Axitinib Inlyta Axitinib

    Trial 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

    Name Type Description Interventions
    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. 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Radiographic tumor response (i.e. maximum tumor shrinkage)

    Secondary Outcome Measures

    Audiologic response

    Trial Keywords

    Neurofibromatosis Type 2

    Vestibular Schwannomas

    Axitinib