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
Overview
- Phase
- Phase 1
- Intervention
- Sorafenib dose escalation
- Conditions
- Glioblastoma
- Sponsor
- University Hospital, Geneva
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy
- Status
- Completed
- Last Updated
- 11 years ago
Overview
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 Description
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.
Investigators
Andreas F. Hottinger
Principal Investigator
University Hospital, Geneva
Eligibility Criteria
Inclusion Criteria
- •Histological documentation of newly diagnosed malignant glioma
- •ECOG performance status of 0 or 1
- •Life expectancy of at least 12 weeks
- •Hemoglobin ≥ 9.0 g/dl
- •Granulocyte count ≥1.5 X 10\^9/L
- •Platelet count ≥100 X 10\^9/L
- •SGOT ≤ 2.5X upper limit of normal (ULN)
- •SGPT ≤ 2.5X upper limit of normal (ULN)
- •Alkaline phosphatase ≤4x ULN
- •Serum creatinine ≤1.5X ULN
Exclusion Criteria
- •Prior treatment for high grade glioma
- •Previous exposure to Ras pathway inhibitors
- •Other concurrent active malignancy (with the exception of cervical carcinoma in situ or non melanoma carcinoma of the skin, superficial bladder tumor \[Ta, Tis \& T1\] or any cancer curatively treated \> 3 years prior to study entry).
- •Serious medical or psychiatric illness that would, in the opinion of the investigator, interfere with the prescribed treatment, including but not limited to: Congestive heart failure \> NYHA class 2, active CAD, cardiac arrythmias requiring anti-arrythmic therapy or uncontrolled hypertension within the last 12 months
- •Any condition limiting the patient's judgment capacity
- •History of HIV infection, chronic hepatitis C or B as well as clinically active infections (\> grade 2 NCI-CTC version 3.0)
- •History of organ allograft
- •Renal dialysis
- •Evidence or history of bleeding diathesis
- •Major surgery within 4 weeks of start of study treatment, except for neurosurgical resection
Arms & Interventions
Sorafenib dose titration
Intervention: Sorafenib dose escalation
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Overall survival(20 months)
- Maximum Observed Plasma Concentration (Cmax) and Area under the curve (AUC) of sorafenib and temozolomide(0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post dose)
- Response rate(35 weeks)
- Time to treatment failure(20 months)
- 6 month progression-free survival(6 months)
- Event free survival(20 months)