SU5416 in Treating Patients With Recurrent Astrocytoma or Mixed Glioma That Has Not Responded to Radiation Therapy
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioma; Astrocytoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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: 
      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.
    

Intervention name(s): semaxanib
Intervention type(s): Drug
Intervention MeSH terms: Semaxinib
Primary purpose: Treatment
Keywords: 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