Clinical Trial: Sorafenib in Newly Diagnosed High Grade Glioma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I Dose Finding Study of Sorafenib in Combination With Radiation Therapy and Temozolomide as a First Line Treatment of Patients With High Grade Glioma

Brief Summary: This is a phase I study to evaluate the safety and tolerability of Sorafenib in combination with Temodar and radiation therapy in patients with newly diagnosed high grade glioma (glioblastoma, gliosarcoma, anaplastic astrocytoma and anaplastic oligodendroglioma or oligoastrocytoma). The mechanism of action of sorafenib, an oral multikinase inhibitor, makes it an interesting drug to investigate in the treatment of patients with high grade glioma as this agent has anti-angiogenic activity and inhibits other pathways such as Ras, Platelet-derived growth factor (PDGF) and fms-like tyrosine kinase receptor-3 (Flt-3), which are potential targets against gliomas.

Detailed Summary: Up to 18 patients will be included in this phase I study. The primary goal of this study will be to establish the maximum tolerated dose of sorafenib when used in combination with temozolomide and radiation therapy. Secondary goals of this study include: response rate, time to treatment failure, 6 month progression-free survival, event free survival and overall survival. A correlative study will investigate the pharmacokinetics of sorafenib used in combination with radiation therapy and temozolomide.
Sponsor: University Hospital, Geneva

Current Primary Outcome: Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy [ Time Frame: 35 weeks ]

Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy in patients with newly diagnosed high grade glioma


Original Primary Outcome: To evaluate safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy in patients with newly diagnosed high grade glioma [ Time Frame: 35 weeks ]

Current Secondary Outcome:

  • Maximum Observed Plasma Concentration (Cmax) and Area under the curve (AUC) of sorafenib and temozolomide [ Time Frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post dose ]
  • Response rate [ Time Frame: 35 weeks ]
  • Time to treatment failure [ Time Frame: 20 months ]
  • 6 month progression-free survival [ Time Frame: 6 months ]
  • Event free survival [ Time Frame: 20 months ]
  • Overall survival [ Time Frame: 20 months ]


Original Secondary Outcome:

  • Pharmacokinetic of sorafenib and temozolomide [ Time Frame: 35 weeks ]
  • Response rate [ Time Frame: 35 weeks ]
  • Time to treatment failure [ Time Frame: 35 weeks ]
  • 6 month progression-free survival [ Time Frame: 35 weeks ]
  • Event free survival [ Time Frame: 35 weeks ]
  • Overall survival [ Time Frame: 35 weeks ]


Information By: University Hospital, Geneva

Dates:
Date Received: April 17, 2009
Date Started: March 2009
Date Completion:
Last Updated: October 31, 2014
Last Verified: October 2014