Study of Sunitinib Before and During Radiotherapy in Newly Diagnosed Biopsy-only Glioblastoma Patients
Condition: Glioblastoma
MeSH terms: Glioblastoma
Study type: Interventional
Phase: Phase 2

Summary: 
      Sunitinib seems to be a promising treatment for the objective of this proposal: to evaluate
      the clinical activity of Sunitinib as first line therapy in patients who have measurable
      disease and to evaluate the safety of Sunitinib with radiation therapy.
    

Detailed description: 
      Sunitinib (SU 11248) is a small molecule with good oral bioavailability that inhibits
      multiple receptor tyrosine kinases (RTKs) expressed on diverse tumour cells: VEGFR, PDGFR,
      KIT, FLT3 and endothelium, pericytes, and stroma VEGFR, PDGFR. It has the potential to
      inhibit directly the growth of multiple tumour types by the inhibition of multiple targets
      and to act negatively on antiangiogenesis.

      Glioblastoma (GB) is the most frequent brain tumour. Standard treatment after surgical
      resection is radiation therapy with Temozolomide. But patients who can afford only a biopsy
      of their lesion due to the location in eloquent areas of their tumour or multifocality, don't
      get benefit from such treatment and their median survival is in the best case of only 9
      months. These patients constitute 30% of Glioblastomas. Clinical trials in this setting are
      required as patients should be treated immediately after the biopsy to prevent neurological
      deterioration.

      These patients are ideal to test new promising therapies. Their survival is similar to
      recurrent patients. The evaluation of response is easier as it's possible to avoid the
      confounding post-surgical changes that interfere with the evaluation of treatment efficacy in
      terms of tumour size reduction.. Furthermore, neo adjuvant treatment before radiotherapy has
      shown not to worsen their survival.

      Glioblastoma is a tumour rich in molecular abnormalities. PDGFRs are important in growth
      signalling pathways and neoangiogenesis of gliomas. PDGF ligands and PDGFR-alfa are expressed
      in most human gliomas, while PDGFR-beta is expressed in glioma cells and tumor endothelial
      cells, PDFGR-α is expressed in most human gliomas. Imatinib mesylate exhibited antiglioma
      activity in preclinical studies, sensitizes glioma cells to radiation injury, and combined
      with hydroxyurea has shown promising results in the recurrent setting.

      Moreover gliomas are among the most angiogenic cancers. VEGF/VEGFR-2 is the most prominent
      angiogenic signalling pathway. Its inhibition either by a neutralizing anti-VEGF antibody,
      anti-sense VEGF constructs, expression of a dominant-negative mutant form of VEGFR-2 (a
      specific small molecule inhibitor of the VEGFR-2 tyrosine kinase) or neutralizing
      anti-VEGFR-2 antibody has resulted in suppression of experimental malignant glioma growth.
      VEGF has been the focus in the development of glioma-targeted therapies. Recently Bevacizumab
      has shown to be active in phase II studies.

      For these reasons, Sunitinib seems to be a promising treatment fo The objective of this
      proposal is to evaluate the clinical activity of Sunitinib as first line therapy in patients
      who have measurable disease and to evaluate the safety of Sunitinib with radiation therapy.
    

Intervention name(s): Sunitinib; Radiation
Intervention type(s): Drug; Radiation
Intervention description(s): Sunitinib 37.5mg/m2/d; Radiation therapy (60Gy) 2 Gy per day during 30 days
Intervention MeSH terms: Sunitinib
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Patients with non resectable Glioblastoma who have only a; biopsy as surgical treatment