| Study Summary: |
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OBJECTIVES:
Primary
- To evaluate the activity of sunitinib malate in patients with recurrent meningioma as
measured by 6-month progression-free survival.
Secondary
- To describe the response rate, median time-to-progression, and overall survival in
these patient.
- To evaluate the safety of sunitinib malate in patients with recurrent meningioma.
Exploratory
- To develop exploratory data correlating response to the molecular phenotype of the
tumor.
- To develop exploratory data correlating serum angiogenic peptides, circulating
endothelial cells (CEC) and circulating progenitor cells (CEP), and Dynamic Contrast
Enhanced (DCE)-MRI with outcomes.
OUTLINE: This is a multicenter study. Patients are stratified according to histology (benign
vs malignant) and whether or not they have neurofibromatosis type 2 (yes vs no).
Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6
weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 1 month and then periodically
thereafter.
PROJECTED ACCRUAL: A total of 50 patients (40 patients with meningioma and 10 patients with
hemangiopericytomas/hemangioblastomas) will be accrued for this study.
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| Criteria: |
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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
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