Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma
Condition: Childhood Cerebellar Anaplastic Astrocytoma; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma
MeSH terms: Glioma; Astrocytoma; Ependymoma; Oligodendroglioma; Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial studies how well sunitinib malate works in treating younger patients with
      recurrent, refractory, or progressive malignant glioma or ependymoma. Sunitinib malate may
      stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To estimate the objective response rate (partial response [PR] or complete response [CR] ≥
      8 weeks) to sunitinib in 2 strata (recurrent/progressive/refractory high-grade glioma vs
      ependymoma) of recurrent or progressive brain tumors in pediatric and young adult patients.

      SECONDARY OBJECTIVES:

      I. To explore and report descriptively the safety and tolerability of sunitinib in pediatric
      and young adult brain tumor patients who have not received prior anthracycline or
      radiotherapy involving the heart.

      II. To describe the pharmacokinetic profile of pediatric and young adult patients taking
      sunitinib malate.

      III. To describe the cumulative toxicities of sunitinib when administered over multiple
      courses to pediatric and young adult patients.

      IV. To estimate progression-free survival (PFS) distributions for these cohorts of patients.

      V. To evaluate changes in phosphorylation of PDGFR-α and -β, MEK/ERK, S6 kinase, and AKT in
      peripheral blood mononuclear cells and explore possible associations between these changes
      and outcome measures.

      VI. To evaluate plasma levels of soluble isoforms of VEGFR-1 and -2 prior to initiation of
      therapy and at points during therapy as an exploration of possible biomarkers of clinical
      response.

      VII. To evaluate and report descriptively the expression and ratio of VEGF isoforms in tumor
      tissue, as available.

      VIII. To evaluate and report descriptively the genotype, expression, and possible
      amplification of KIT and PDGFR-α and -β in tumor tissue, as available.

      OUTLINE: This is a multicenter study.

      Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28. Treatment repeats
      every 42 days for up to 18 courses in the absence of disease progression or unacceptable
      toxicity.

      Patients may undergo blood sample collection at baseline and during courses 1 and 2 for
      pharmacokinetic and pharmacodynamic studies. Tissue samples from diagnosis and surgical
      resection may be also collected.

      After completion of study treatment, patients are followed up for up to 5 years.
    

Intervention name(s): Diagnostic Laboratory Biomarker Analysis; Pharmacological Study; Sunitinib Malate
Intervention type(s): Other; Other; Drug
Intervention description(s): Correlative studies; Correlative studies; Given PO
Other intervention name(s): SU011248; SU11248; sunitinib; Sutent
Intervention MeSH terms: Sunitinib
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment