Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Adenocarcinoma

Glioblastoma

Brain Neoplasms

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Antisickling Agents

Amino Acids

Temozolomide

Hydroxyurea

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Every 6 weeks after randomization based on assessment of therapeutic response, either patients continued with above mentioned dosing regimen or switched to receive a daily dose of 800 mg imatinib with 1000 mg HU. Patients were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening.

1500 mg/day of HU given as 500 mg 3 times daily. Every 6 weeks after randomization and based on assessment of therapeutic response, the patients were either switched to combination arm or continued in monotherapy arm of hydroxyurea.

Imatinib was supplied as 100 mg and 400 mg tablets packaged in polyethylene bottles.

Imatinib mesylate

Novartis Pharmaceuticals

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

Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma

Phase III Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma

PFS was defined as the time from the date of randomization to the date of the first documented progression according to the MacDonald criteria, or death due to any cause. MacDonald criteria are standard criteria in neurooncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).

National Cancer Institute (NCI)/ National Institute of Health (NIH) provides a grading (severity) scale for each AE term. Grade 3 refers to severe AE and Grade 4 refers to life-threatening or disabling AE. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening ( NIH criteria Grade 4), causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.

External Affairs

Safety population = patients who were randomized to either Imatinib + Hydroxyurea (combination)\[n=118\] or to Hydroxyurea alone \[n=118\]. Every 6 wks, patients on Hydroxyurea alone switched to combination arm depending on response. So, for the safety analysis Hydroxyurea arm is divided into Hydroxyurea alone \[n=118\] or switch to combination \[n=85\].

Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Patients receiving a daily dose of 800 mg imatinib with 1000 mg HU were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening.

Imatinib Mesylate + Hydroxyurea (HU)

1500 mg/day of HU given as 500 mg 3 times daily.

Period With Hydroxyurea Alone

After every 6 weeks from randomization, depending on the assessment of therapeutic effect, patients were switched from Hydroxyurea (1500 mg/day p.o) to combination arm where patients were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time).

Period After Switch to Combination

Hydroxyurea Alone

Total

Age Continuous

Sex: Female, Male

Study Director

6 months

12 months

The ITT population consists of all randomized patients, analyzed according to their randomized treatment.

Percentage of Participants With Progression Free Survival (PFS) During the Study Duration

Deaths

Death due to disease progression

Serious Adverse Events (SAEs)

NCI/NIH Grade 3 (severe) or 4 (life threatening)

Suspected to be drug-related

Leading to dose adjustment or interruption

Leading to permanent discontinuation

The safety population consisted of randomized patients with at least one dose of randomized medication.

Number of Participants With Death, Other Serious or Clinically Significant Adverse Events (AEs) or Related Discontinuations

Overall Study

Spots Global Cancer Trial Database for Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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