Clinical trial NCT00154375: Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
Official title: Phase III Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glioblastoma Multiforme
Astrocytoma
Keywords: Open label
Imatinib mesylate
hydroxyurea
temozolomide
resistant
protein tyrosine kinases
adenocarcinoma
glioblastoma multiforme
astrocytoma
brain tumor
brain cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Percentage of Participants With Progression Free Survival (PFS) During the Study Duration
timeFrame: 6 months -1 year
Secondary outcomes:
measure: Number of Participants With Death, Other Serious or Clinically Significant Adverse Events (AEs) or Related Discontinuations
timeFrame: 6 months - 1 year
Other outcomes:
Locations:
city: Duelmen
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: