Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
Condition: Glioblastoma Multiforme; Astrocytoma
MeSH terms: Glioblastoma; Astrocytoma
Intervention: Imatinib mesylate; Hydroxyurea
Intervention description: Imatinib was supplied as 100 mg and 400 mg tablets packaged in polyethylene bottles.
Intervention MeSH terms: Imatinib Mesylate; Hydroxyurea
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 240.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Open label; Imatinib mesylate; hydroxyurea; temozolomide; resistant; protein tyrosine kinases; adenocarcinoma; glioblastoma multiforme; astrocytoma; brain tumor; brain cancer

Summary:

      This is a Phase III study comparing Imatinib mesylate and hydroxyurea combination therapy
      with hydroxyurea monotherapy in patients with temozolomide resistant progressive
      glioblastoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        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.

          -  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.