Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
Overview
- Phase
- Phase 2
- Intervention
- Sunitinib
- Conditions
- CNS Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 50
- Locations
- 6
- Primary Endpoint
- Overall Objective Response
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief 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.
Detailed Description
This is a phase II study of Sunitinib in patients with recurrent or inoperable meningiomas. An exploratory study will be performed for patients with recurrent hemangiopericytoma or hemangioblastoma. There will be approximately 50 patients enrolled on this study (40 meningiomas and 10 hemangiopericytomas/hemangioblastomas). The treatment plan is to use daily SU11248 at a dose of 50 mg, using the established schedule of 4 weeks of treatment followed by two weeks of rest period, forming a six-week treatment cycle. A medical professional will see each patient at least every six weeks while on the medication for toxicity assessment and physical examination. Extent of disease evaluations will occur at baseline, two weeks, twelve weeks, 24 weeks, and every twelve weeks thereafter. These evaluations will include MRI of the brain (or CT head if a patient cannot undergo MRI) and MR perfusion.
Investigators
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
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 ≥
- •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.
Arms & Interventions
Treatment
Sunitinib will be administered at a dose of 50 mg orally once daily for four consecutive weeks, followed by a two-week rest period. Intra-patient dose reduction may be required depending on the type and severity of individual toxicity encountered. Imaging studies will be performed after every other cycle. Patients may continue on study as long as they are tolerating treatment and in the absence of disease progression.
Intervention: Sunitinib
Outcomes
Primary Outcomes
Overall Objective Response
Time Frame: 1.5 years
Determine the overall objective response