This is a Phase III study comparing Imatinib mesylate and hydroxyurea combination therapy
with hydroxyurea monotherapy in patients with temozolomide resistant progressive
glioblastoma.
Inclusion Criteria
- Signed informed consent prior to initiation of any study procedure.
- Patients >= 18 years of age.
- Histological confirmed diagnosis of glioblastoma multiforme / astrocytoma WHO grade IV
by a reference pathologist
- ECOG Performance Status of 0, 1 or 2. [Appendix 2]
- Adequate hepatic, renal and bone marrow function as defined by the following: total
bilirubin =< 1. 5 x ULN, SGOT and SGPT =< 2. 5 x ULN, creatinine =< 1. 5 x ULN, ANC >=
1. 5 x 109/L, platelets >= 100 x 109/L and Hgb >10g/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 MRT must be performed.
Exclusion Criteria
- 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 [Appendix 3].
- Patients with other malignant disorders.
- Patient with acute or known chronic liver disease (i. e., chronic active hepatitis,
cirrhosis).
- 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
schedule
- 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
drug.
Other protocol-specific inclusion /exclusion criteria may apply.
