Phase III Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
- Signed informed consent prior to initiation of any study procedure.
- Patients >= 18 years of age.
- Histological confirmed diagnosis of glioblastoma multiforme / astrocytoma World
Health Organization (WHO) grade IV by a reference pathologist
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
- Adequate hepatic, renal and bone marrow function as defined by the following: total
bilirubin < 1.5 x Upper Limit of Normal (ULN), ALT and AST < 2.5 x ULN, creatinine <
1.5 x ULN, absolute neutrophil count > 1.5 x109/L, platelets > 100 x109/L and
hemoglobin > 10 g/dL.
- Female patients of childbearing potential with a negative pregnancy test within 7
days of initiation of study drug dosing. Postmenopausal women must be amenorrheic for
at least 12 months to be considered of non-childbearing potential. Male and female
patients of reproductive potential who agree to employ an effective barrier method of
birth control throughout the study, and for up to 3 months following discontinuation
of study drug.
- Life expectancy of >3 months.
- MRI available every 6 weeks for disease management
- No intercerebral inflammation
- Irradiation therapy 54 to 62 gy finished or less according to national standard
- Chemotherapy at least 1 temozolomide containing regimen finished, no established
chemotherapy regiment available and progression under chemotherapy or in between 6
months following the last chemotherapy.
- Leucocytes > 2.500/µl, to be controlled once a week
- Thrombocytes > 80.000/µl, to be controlled once a week
- Ensured compliance
- Patients who had a second or third resection after disease progression cannot be
included earlier than 2 weeks following the resection. MRI should be performed not
later than 72 h post operation. If patients are to be included later than 4 weeks
after the resection, a new baseline MRI must be performed.
- Female patients who are pregnant or breast-feeding.
- Patients who have been treated with any investigational agent(s) within 28 days of
the first day of administration of study drug.
- Patients with uncontrolled medical disease such as diabetes mellitus, thyroid
dysfunction, neuropsychiatric disorders, infection, angina or Grade 3 or 4 cardiac
problems as defined by the New York Heart Association Criteria.
- Patients with other malignant disorders.
- Patient with acute or known chronic liver disease (i.e., chronic active hepatitis,
- Patients who are known to be HIV positive (no specific tests are required for
confirmation of eligibility).
- Expected incompliance according to treatment, treatment diary and examination
- Not confirmed histological diagnosis glioblastoma multiforme/astrocytoma WHO grade IV
- Other drugs with potential cytostatic main or side effect
- No or inadequate chemotherapy or irradiation therapy
- Patients without hematological recovery after previous chemotherapy who have been
treated with Chemotherapy within 28 days of the first day of administration of study
Other protocol-specific inclusion /exclusion criteria may apply.