SU5416 in Treating Patients With Recurrent Astrocytoma or Mixed Glioma That Has Not Responded to Radiation Therapy

Study Overview
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Brief Summary
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RATIONALE: SU5416 may stop the growth of astrocytoma or glioma by stopping blood flow to the tumor. PURPOSE: Phase I/II trial to study the effectiveness of SU5416 in treating patients who have recurrent astrocytoma or mixed glioma that has not responded to previous radiation therapy.

Detailed Description
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OBJECTIVES: Phase I: Determine the maximum tolerated dose of SU5416 in patients with recurrent malignant glioma who are, as well as those who are not, taking enzyme-inducing antiepileptic drugs. Determine the toxic effects (safety profile) of this drug in this patient population. Characterize the pharmacokinetics of this drug in these patients. Develop exploratory data relative to surrogate endpoints of angiogenic activity in vivo, including functional imaging and in vitro assays of endothelial cell inhibition and serum angiogenic peptides. Phase II: Determine the efficacy of SU5416, in terms of 6-month progression-free survival, in patients with recurrent high-grade glioma. Determine, further, the safety profile of the phase II dose of this drug in this patient population. Develop exploratory data relative to surrogate endpoints of angiogenic activity in vivo including functional imaging and in vitro assays of endothelial cell inhibition and serum angiogenic peptides. OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent enzyme-inducing antiepileptic drugs (no vs yes). Patients receive SU5416 IV on days 1 and 4 weekly for 4 weeks. Courses repeat every 4 weeks in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of SU5416 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD has been determined, additional patients are accrued to the phase II portion of the study. These patients receive SU5416 IV, as in the phase I portion, at the appropriate MTD established in phase I. Patients are followed for survival. PROJECTED ACCRUAL: At least 30 patients will be accrued for the phase I dose-escalation portion of this study within 10 months. An additional 48 patients (32 with glioblastoma multiforme and 16 with anaplastic glioma) will be accrued for the phase II portion of this study within 6-8 months.

Official Title
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A Phase I/II Trial of SU5416 in Patients With Recurrent High Grade Astrocytomas or Mixed Gliomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: semaxanib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven supratentorial malignant primary glioma, including: Glioblastoma multiforme Anaplastic astrocytoma Anaplastic oligodendroglioma Anaplastic mixed oligoastrocytoma Malignant astrocytoma not otherwise specified Benign or malignant meningiomas, including brain and spinal meningiomas Patients with meningiomas are excluded from phase II portion of study Must have shown unequivocal evidence of tumor recurrence or progression by CT scan or MRI Must have failed prior radiotherapy Must have prestudy contrast MRI or contrast CT scan of brain on stable steroid dose within the past 14 days Must be on stable (unchanged) dose of steroids for at least 5 days before scans Phase II: Must have completed radiotherapy at least 2 months prior to enrollment PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: More than 8 weeks Hematopoietic: WBC at least 2,300/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 8 g/dL (transfusion allowed) Hepatic: SGOT less than 2.5 times upper limit of normal Bilirubin normal No significant active hepatic disease Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min No significant active renal disease Cardiovascular: No uncompensated coronary artery disease on ECG or physical examination No history of myocardial infarction or severe/unstable angina within the past 6 months No deep venous or arterial thrombosis within the past 3 months Pulmonary: No pulmonary embolism within the past 3 months Other: Not pregnant or nursing Fertile patients must use effective contraception during and for 2 months after study No other serious concurrent illness No significant active psychiatric disease No diabetes mellitus with severe peripheral vascular disease No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No serious active infection No other concurrent disease that would obscure toxic effects or dangerously alter drug metabolism PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior biologic therapy (e.g., interferon) and recovered No concurrent immunotherapy Chemotherapy: Phase I: No more than 2 prior chemotherapy regimens for recurrent disease Phase II: No more than 1 prior chemotherapy regimen for recurrent disease At least 2 weeks since prior vincristine At least 6 weeks since prior nitrosoureas At least 3 weeks since prior procarbazine Recovered from prior chemotherapy No concurrent chemotherapy Endocrine therapy: See Disease Characteristics At least 3 weeks since prior endocrine therapy (e.g., tamoxifen) and recovered Radiotherapy: See Disease Characteristics No concurrent radiotherapy Surgery: Recovered from prior surgery Recent prior resection of recurrent or progressive tumor allowed Other: No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: semaxanib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult brain tumor, adult meningioma, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult grade III meningioma, adult giant cell glioblastoma, adult gliosarcoma