Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed meningioma or intracranial hemangiopericytoma or
hemangioblastoma

- Recurrent or unresectable disease

- Benign, atypical, or malignant meningioma

- Neurofibromatosis (NF) type 1 or type 2 allowed

- Classic radiographic picture of meningioma allowed provided the tumor is not
surgically accessible

- Must undergo review at a multidisciplinary brain tumor conference including
neurosurgery and neuroradiology to determine that the patient is appropriate for
this study

- Unequivocal evidence of tumor progression by MRI or CT scan

- Patients with malignant meningioma must be on a stable dose of steroids for at least
5 days prior to baseline imaging

- Patients with benign or atypical meningioma are not required to be on a stable
dose of steroids

- Patients who have not had prior surgery or radiotherapy for meningioma will be
reviewed at a multidisciplinary brain tumor conference including neurosurgery and
radiation oncology to determine that the patient is appropriate for this study

- Patients with a history of NF may have other stable CNS tumors (e.g., schwannoma,
acoustic neuroma, or ependymoma) provided those lesions have been stable in size for
the past 6 months

PATIENT CHARACTERISTICS:

Inclusion criteria:

- Karnofsky performance status ≥ 60%

- Absolute neutrophil count (ANC) ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 8 g/dL

- Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) ≤
2.5 x upper limit of normal (ULN)

- Serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x
ULN

- Creatinine ≤ 2.0 mg/dL

- PT, INR, and PTT ≤ 1.5 x ULN

- Total serum bilirubin ≤ 1.5 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Women must be surgically sterile, postmenopausal, or agree to use effective
contraception during study therapy and men must be surgically sterile or agree to use
effective contraception

- Patients who have not had prior surgery or radiotherapy for their meningioma will be
reviewed at a multidisciplinary brain tumor conference including neurosurgery and
radiation oncology to determine that the patient is appropriate for this study

Exclusion criteria:

- History of any other cancer, except nonmelanoma 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

- Any of the following within the past 6 months:

- Myocardial infarction

- Severe/unstable angina

- Coronary/peripheral artery bypass graft

- Symptomatic congestive heart failure

- Cerebrovascular accident or transient ischemic attack

- Pulmonary embolism

- Ongoing cardiac dysrhythmias ≥ grade 2 by NCI CTCAE Version 3.0

- Prolonged QTc interval on baseline EKG (> 450 msec for males or > 470 msec for
females)

- Uncontrolled hypertension (> 150/100 mm Hg despite optimal medical therapy), elevated
diastolic blood pressure (BP), systolic BP 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), acquired immunodeficiency syndrome
(AIDS)-related illness, or other active infection

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

- See Disease Characteristics

- At least 4 weeks since prior standard external beam radiotherapy , interstitial
brachytherapy, or radiosurgery in any combination 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

- At least 4 weeks since prior radiotherapy, radiosurgery, or chemotherapy

- There is no limitation on the number of prior surgeries, radiotherapy,
radiosurgery treatments, or chemotherapy

- Recent resection for recurrent tumor allowed provide the patient has recovered from
the effects of surgery and has residual disease that can be evaluated

- CT scan/MRI should be done no later than 96 hours in the immediate postoperative
period or at least 4 weeks post-operatively

- If the 96 hour scan is more than 14 days before registration, it should be
repeated

- Must wait at least 14 days after surgery, without complications, before start of
study treatment

Exclusion criteria:

- Any prior tyrosine kinase inhibitor therapy (i.e., SU011248, sorafenib, semaxinib, or
axitinib)

- Any other concurrent investigational drugs

- Concurrent enzyme-inducing antiepileptic drugs

- Concurrent St. John's wort

- Concurrent treatment on another clinical trial except supportive care trials or
non-treatment trials (e.g., quality of life studies)

- Concurrent therapeutic doses of warfarin

- Concurrent low dose warfarin (≤ 2 mg/day) for thromboembolic prophylaxis is
allowed