Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
Condition: CNS Cancer; Meningioma; Intracranial Hemangiopericytoma; Hemangioblastoma; Neurofibromatosis
MeSH terms: Meningioma; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Hemangiopericytoma; Solitary Fibrous Tumors; Hemangioblastoma; Central Nervous System Neoplasms
Intervention: Sunitinib
Intervention description: The study drug will be administered on an outpatient basis. The starting dose will be 50 mg daily for 28 days (4 consecutive weeks) followed by 14 days off for patients not on CYP3A4 inducers or inhibitors. A cycle equals 42 days.
Intervention MeSH terms: Sunitinib; Cytochrome P-450 CYP3A Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Sunitinib; Brain Cancer; CNS Cancer; meningioma; intracranial hemangiopericytoma; hemangioblastoma; malignant meningioma; neurofibromatosis; neurofibromatosis type 1; neurofibromatosis type 2; 07-135

Summary:

      The purpose of this study is to find out what effects, good and/or bad, sunitinib has on
      patients and their tumors. At this time, no drugs are routinely used to treat meningioma,
      hemangioblastoma or hemangiopericytoma. Only surgery and radiation therapy are known to be
      useful.

      Sunitinib is a drug approved for advanced kidney cancer. Sunitinib is also being studied for
      other tumors. It may be useful in the treatment of brain tumors because it can prevent
      formation of new blood vessels that allow tumor cells to survive and grow.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven recurrent meningioma or intracranial hemangiopericytoma or
             hemangioblastoma. This includes benign, atypical, or malignant meningioma; patients
             with neurofibromatosis type 1 or 2 may participate.

          -  Patients with classic radiographic picture of meningioma may also enroll if not
             surgically accessible. In this instance the patient must be reviewed at
             multi-disciplinary brain tumor conference including neurosurgery and neuroradiology to
             determine that the patient is appropriate for this study.

          -  Unequivocal evidence for tumor progression by MRI (or CT scan if MRI is
             contraindicated). The scan must be performed within 14 days of registration.

          -  Steroids dosing - malignant meningiomas must be on stable dose for at least 5 days
             prior to baseline imaging. For patients with benign or atypical meningiomas, stable
             steroid doses are not required.

          -  Recent resection for recurrent tumor - patients will be eligible as long as they have
             recovered from the effects of surgery and have residual disease that can be evaluated.
             To best assess the extent of residual disease post-operatively, a CT/MRI should be
             done no later than 96 hours in the immediate post-operative period or at least 4 weeks
             post-operatively. If the 96 hour scan is more than 14 days before registration, it
             should be repeated. Because Sunitinib is a VEGF inhibitor that can carry many risks
             including thrombocytopenia, bleeding, hypertension, and stroke, patients must wait at
             least 14 days after surgery, without complication, before they may initiate study
             drug.

          -  Prior radiation therapy - patients may have been treated with standard external beam
             radiation, interstitial brachytherapy, or radiosurgery in any combination. An interval
             of ≥ 4 weeks (28 days) must have elapsed from the completion of radiation therapy to
             study entry and there must be subsequent evidence of tumor progression. Patients with
             prior interstitial brachytherapy or stereotactic radiosurgery must have confirmation
             of true progressive disease rather than radiation necrosis based on PET, MR
             spectroscopy or surgical documentation of disease.

          -  Patients who have not had prior surgery or radiotherapy for their meningioma will be
             reviewed at multi-disciplinary brain tumor conference including neurosurgery and
             radiation oncology to determine that the patient is appropriate for this study.

          -  Prior therapy: There is no limitation on the number of prior surgeries, radiation
             therapy, radiosurgery treatments, or chemotherapy.

          -  All patients must sign an informed consent indicating that they are aware of the
             investigational nature of the study. Patients must sign an authorization for the
             release of their protected health information.

          -  Age ≥ 18 years old

          -  Karnofsky performance status ≥ 60%.

          -  ≥ 4 weeks since prior RT, stereotactic radiosurgery, or chemotherapy.

          -  Required Initial Laboratory Values (within 14 days of registration):

        Absolute neutrophil count (ANC) ≥ 1,000/mm3

          -  Platelets ≥ 100,000/mm3

          -  hemoglobin ≥ 8gm/dl

          -  Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and
             serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x
             local laboratory upper limit of normal (ULN)

          -  Creatinine ≤ 2.0 mg/dl

          -  PT, INR, and PTT ≤ 1.5 times institutional upper limits of normal

          -  Total serum bilirubin ≤ 1.5 - Patients with a history of NF may have other stable CNS
             tumors, such as schwannoma, acoustic neuroma, or ependymoma, but ONLY if these lesions
             have been stable in size for the preceding 6 months.

        Exclusion Criteria:

          -  Patients with the history of any other cancer (except non-melanoma skin cancer or
             carcinoma in-situ of the cervix, unless in complete remission and off all therapy for
             the disease for a minimum of 3 years) are ineligible.

          -  Any prior TKI therapy (SU011248, Sorafenib, Semaxinib, Axitinib)

          -  Concomitant use of any other investigational drugs

          -  Concomitant use of enzyme-inducing anti-epileptic drugs.

          -  Concomitant use of St John's Wort.

          -  Any of the following within the 6 months prior to study drug administration:
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
             graft, symptomatic congestive heart failure, cerebrovascular accident or transient
             ischemic attack, or pulmonary embolism.

          -  Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade ≥ 2.

          -  Prolonged QTc interval on baseline EKG (>450 msec for males and >470 msec for
             females).

          -  Uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy). Patients
             are excluded if they have an elevated diastolic, an elevated systolic, or both.

          -  History of intracranial hemorrhage.

          -  Pre-existing thyroid abnormality, with thyroid function tests that cannot be
             maintained in the normal range with medication.

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness or other active infection.

          -  Concurrent treatment on another clinical trial. Supportive care trials or
             non-treatment trials, e.g. QOL, are allowed.

          -  Ongoing treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg
             daily for thromboembolic prophylaxis is allowed).

          -  Pregnancy or breast-feeding. Patients must be surgically sterile, postmenopausal, or
             agree to use effective contraception during the period of therapy. The definition of
             effective contraception will be based on the judgment of the principal investigator or
             a designated associate. Male patients must be surgically sterile or agree to use
             effective contraception. Women of childbearing potential must have a negative B-HCG
             pregnancy test documented within 14 days prior to registration.