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
- Histological documentation of newly diagnosed malignant glioma
- ECOG performance status of 0 or 1
- Age ≥18
- 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
- Bilirubin ≤1.5X ULN
- Spontaneous PT-INR/PTT < 1.5x upper limit of normal (patients on therapeutic
anticoagulation will be allowed to participate.
- Patients must be on a stable or decreasing dose of corticosteroids for at least 2
- Patient for whom a first line treatment with temozolomide and radiotherapy is
- Prophylactic anti-emetic, pentamidine inhalation / co-trimoxazole and anticonvulsants
- All patients must sign written informed consent.
- 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
- Autologous bone marrow transplant or stem cell rescue within 4 months of study
- Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of study results.
- Medical condition that prevents the patient from swallowing pills
- Use of biologic response modifiers, such as G-CSF within 3 week of study entry.
- Pregnant or breast-feeding women.
- Refusal to use effective contraception. Women of childbearing potential must have a
negative pregnancy test performed within 7 days of the start of treatment. Both men
and women enrolled in this trial must use adequate barrier birth control measures
during the course of the trial and for at least 3 months after administration of
- Known or suspected allergy to the investigational agent or any agent given in
association with this trial.