A Phase II, Open-label, Multicenter Study Evaluating the Efficacy of Imatinib Plus Hydroxyurea (HU) in Patients With Progressive Glioblastoma Multiforme (GBM) Receiving or Not Receiving Enzyme-inducing Anticonvulsant Drugs (EIACDs)
Overview
- Phase
- Phase 2
- Intervention
- Imatinib tablets
- Conditions
- Recurrent Glioblastoma Multiforme (GBM)
- Sponsor
- Novartis
- Enrollment
- 231
- Locations
- 1
- Primary Endpoint
- Percentage of Patients With an Objective Overall Response (OOR)
- Status
- Terminated
- Last Updated
- 14 years ago
Overview
Brief Summary
This was an investigational study to assess the objective overall response (OOR) rate (complete response [CR] + partial response [PR]) of imatinib mesylate and hydroxyurea (hydroxycarbamide) combination therapy in patients with recurrent glioblastoma multiforme (brain tumors). This study also evaluated the duration of tumor response (as per MacDonald criteria), clinical benefit, progression-free survival rate at 6 and 12 months, and the survival rate at 12 and 24 months.
Detailed Description
This ClinicalTrials.gov record includes the results from two studies (Novartis protocol IDs CSTI571H2201 and CSTI571H2202) which were conducted separately but reported together in a single clinical study report. Both studies were phase II, open-label, multicenter, single-arm studies that evaluated the efficacy of imatinib mesylate plus hydroxyurea in subjects with progressive glioblastoma multiforme. The studies were identical in design with two exceptions: Patients in study CSTI571H2201 received a dose of imatinib 600 mg once daily and were not allowed concomitant use of enzyme-inducing anticonvulsant drugs (EIACDs); patients in study CSTI571H2202 received a dose of imatinib 500 mg twice daily and were allowed concomitant use of EIACDs.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Receipt of imatinib or hydroxyurea (HU) prior to study entry or receipt of any investigational agent within the last 6 months.
- •Patients who had received a second course of chemotherapy or radiotherapy, unless given as a single localized application of radio surgery.
- •In study STI571H2201 only, receipt of enzyme-inducing anticonvulsant drugs (EIACDs), eg, carbamazepine, phenobarbital, phenytoin, fosphenytoin, oxcarbazepine, or primidone. Previous EIACD should have been interrupted 4 weeks prior to study start.
- •Grade ≥ 2 peripheral edema or pulmonary or pericardial effusions or ascites of any grade.
- •Presence of any uncontrolled systemic infection.
- •Patients who were not a minimum of 12 weeks from completion of conventional external beam radiotherapy unless:
- •There was new radiographical enhancement outside the field of radiation, or
- •There was new pathological confirmation of recurrent tumor, or
- •Progressive radiographical enhancement noted on post-radiotherapy/TMZ continue to worsen after an additional course of TMZ.
- •Evidence of intra-tumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative Grade 1 hemorrhage, patients with an excessive risk of an intracranial hemorrhagic event, and patients with history of central nervous system (excluding post-operative Grade 1) or intraocular bleed.
Arms & Interventions
Imatinib 600 mg + hydroxyurea 1000 mg
Patients took imatinib 600 mg (1 imatinib 400 mg tablet and 2 imatinib 100 mg tablets) orally once daily with the morning meal. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were not allowed concomitant use of enzyme-inducing anticonvulsant drugs.
Intervention: Imatinib tablets
Imatinib 600 mg + hydroxyurea 1000 mg
Patients took imatinib 600 mg (1 imatinib 400 mg tablet and 2 imatinib 100 mg tablets) orally once daily with the morning meal. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were not allowed concomitant use of enzyme-inducing anticonvulsant drugs.
Intervention: Hydroxyurea capsules
Imatinib 1000 mg + hydroxyurea 1000 mg
Patients took imatinib 500 mg (1 imatinib 400 mg tablet and 1 imatinib 100 mg tablet) orally twice daily with the morning and evening meals. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were allowed concomitant use of enzyme-inducing anticonvulsant drugs.
Intervention: Imatinib tablets
Imatinib 1000 mg + hydroxyurea 1000 mg
Patients took imatinib 500 mg (1 imatinib 400 mg tablet and 1 imatinib 100 mg tablet) orally twice daily with the morning and evening meals. Patients were instructed to swallow the tablets while drinking a large glass of water. In addition to imatinib, patients took hydroxyurea 500 mg orally twice daily with the morning and evening meals. Patients were allowed concomitant use of enzyme-inducing anticonvulsant drugs.
Intervention: Hydroxyurea capsules
Outcomes
Primary Outcomes
Percentage of Patients With an Objective Overall Response (OOR)
Time Frame: Baseline to end of study (Month 24)
Patients with an OOR were those whose best response to treatment was a complete response (CR) or a partial response (PR) assessed with magnetic resonance imaging. A patient had a CR if the target tumors disappeared. A patient had a PR if there was a ≥ 50% reduction in the sum of the products of the largest perpendicular diameters of the target tumors compared to the baseline value. A best response of CR required at least 2 determinations of CR at least 4 weeks apart. A best response of PR required at least 2 determinations of PR or better at least 4 weeks apart (and not qualifying for CR).
Secondary Outcomes
- Duration of Objective Overall Response (OOR)(Baseline to end of study (Month 24))
- Percentage of Patients Who Had Clinical Benefit(Baseline to end of study (Month 24))
- Percentage of Patients With Progression-free Survival at Months 6 and 12(Months 6 and 12)
- Percentage of Patients Surviving at Months 6, 12, and 24(Months 6, 12, and 24)
- Number of Patients With at Least 1 Adverse Event(Baseline to end of study (Month 24))