A Phase 2 interventional study of Imatinib tablets and Hydroxyurea capsules in Recurrent Glioblastoma Multiforme (GBM), sponsored by Novartis. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2011-05-16.
Sponsored by Novartis · Phase 2, Interventional, and Treatment
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.
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.
1,951 studies on the registry are indexed under Glioblastoma; 457 are open to participants now.
This study's enrollment of 231 is above the median of 36 across 1,645 interventional studies indexed under Glioblastoma.
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Exclusion Criteria:
Patients who were not a minimum of 12 weeks from completion of conventional external beam radiotherapy unless:
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.
Drug: Imatinib tablets · Drug: Hydroxyurea capsules
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.
Drug: Imatinib tablets · Drug: Hydroxyurea capsules
Imatinib was supplied as 100 and 400 mg tablets by Novartis.
Also known as: Glivec®
Hydroxyurea was supplied locally as 500 mg capsules.
Percentage of Patients With an Objective Overall Response (OOR)
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).
Time frame: Baseline to end of study (Month 24)
Duration of Objective Overall Response (OOR)
Duration of OOR only included patients whose best overall response was complete response (CR) or partial response (PR). The start date was the date of the first documented response (CR or PR); the end date was the date of the first documented disease progression (PD) or death from any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. If a patient had not progressed or died, the duration of OOR was censored at the time of the last OOR assessment.
Time frame: Baseline to end of study (Month 24)
Percentage of Patients Who Had Clinical Benefit
Patients who had clinical benefit were patients with a best response of complete response (CR), partial response (PR), or stable disease (SD) lasting for more than 6 months from the start of treatment until the first documented disease progression (PD) or death from any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. SD was defined as insufficient tumor shrinkage to qualify for PR or CR and no increase in lesions which would qualify as PD.
Time frame: Baseline to end of study (Month 24)
Percentage of Patients With Progression-free Survival at Months 6 and 12
Progression-free survival (PFS) was defined as the time from the start of treatment to the date of the first documented disease progression (PD) or death due to any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. If a patient had not progressed or died, progression-free survival was censored at the time of the last overall response assessment.
Time frame: Months 6 and 12
Percentage of Patients Surviving at Months 6, 12, and 24
Patients not known to have died were censored at the time of last survival follow-up.
Time frame: Months 6, 12, and 24
Number of Patients With at Least 1 Adverse Event
An adverse event (AE) is any undesirable sign, symptom, or medical condition occurring after starting study drug even if the event is not considered to be related to study drug. Study drug refers to imatinib or hydroxyurea. The study treatment is the combination of these two study drugs.
Time frame: Baseline to end of study (Month 24)
| Milestone | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg |
|---|---|---|
| Started | 131 | 100 |
| Completed | 4 | 3 |
| Not completed | 127 | 97 |
| Withdrew: Disease progression | 95 | 73 |
| Withdrew: Death | 11 | 10 |
| Withdrew: Adverse event | 12 | 6 |
| Withdrew: Withdrawal by subject | 5 | 6 |
| Withdrew: Administrative problems | 2 | 1 |
| Withdrew: Protocol violation | 2 | 0 |
| Withdrew: Lost to follow-up | 0 | 1 |
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).
| Percentage of participants | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg | All Patients - Imatinib 600 or 1000 mg + Hydroxyurea 1000 mg |
|---|---|---|---|
| Percentage of Patients With an Objective Overall Response (OOR) | 3.8 (1.3 to 8.7) | 3.0 (0.6 to 8.5) | 3.5 (1.5 to 6.7) |
Duration of OOR only included patients whose best overall response was complete response (CR) or partial response (PR). The start date was the date of the first documented response (CR or PR); the end date was the date of the first documented disease progression (PD) or death from any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. If a patient had not progressed or died, the duration of OOR was censored at the time of the last OOR assessment.
| Weeks | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg | All Patients - Imatinib 600 or 1000 mg + Hydroxyurea 1000 mg |
|---|---|---|---|
| Duration of Objective Overall Response (OOR) | 41.1 (32.1 to 53.6) | 32.1 (20.1 to NA) | 37.1 (32.1 to 53.6) |
Patients who had clinical benefit were patients with a best response of complete response (CR), partial response (PR), or stable disease (SD) lasting for more than 6 months from the start of treatment until the first documented disease progression (PD) or death from any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. SD was defined as insufficient tumor shrinkage to qualify for PR or CR and no increase in lesions which would qualify as PD.
| Percentage of participants | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg | All Patients - Imatinib 600 or 1000 mg + Hydroxyurea 1000 mg |
|---|---|---|---|
| Percentage of Patients Who Had Clinical Benefit | 9.9 (5.4 to 16.4) | 6.0 (2.2 to 12.6) | 8.2 (5.0 to 12.5) |
Progression-free survival (PFS) was defined as the time from the start of treatment to the date of the first documented disease progression (PD) or death due to any cause. (PD) was defined as ≥ 25% increase in size of the sum of the products of the largest perpendicular diameters of the target tumors compared to the smallest value recorded at or after baseline. If a patient had not progressed or died, progression-free survival was censored at the time of the last overall response assessment.
| Percentage of participants | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg | All Patients - Imatinib 600 or 1000 mg + Hydroxyurea 1000 mg |
|---|---|---|---|
| 6 Months | 11.2 (5.7 to 16.6) | 9.9 (3.8 to 15.9) | 10.6 (6.5 to 14.7) |
| 12 Months | 6.9 (2.4 to 11.3) | 3.3 (0.0 to 6.9) | 5.3 (2.3 to 8.3) |
Patients not known to have died were censored at the time of last survival follow-up.
| Percentage of participants | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg | All Patients - Imatinib 600 or 1000 mg + Hydroxyurea 1000 mg |
|---|---|---|---|
| 6 Months | 49.2 (40.7 to 57.8) | 50.9 (40.9 to 61.0) | 50.0 (43.4 to 56.5) |
| 12 Months | 28.5 (20.7 to 36.2) | 31.3 (21.9 to 40.7) | 29.7 (23.7 to 35.7) |
| 24 Months | 10.7 (3.3 to 18.1) | 20.3 (11.8 to 28.9) | 13.9 (8.0 to 19.7) |
An adverse event (AE) is any undesirable sign, symptom, or medical condition occurring after starting study drug even if the event is not considered to be related to study drug. Study drug refers to imatinib or hydroxyurea. The study treatment is the combination of these two study drugs.
| Participants | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg | All Patients - Imatinib 600 or 1000 mg + Hydroxyurea 1000 mg |
|---|---|---|---|
| Number of Patients With at Least 1 Adverse Event | 129 | 98 | 227 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Imatinib 600 mg + Hydroxyurea 1000 mg | — | 62/131 (47.3%) | 122/131 (93.1%) |
| Imatinib 1000 mg + Hydroxyurea 1000 mg | — | 53/99 (53.5%) | 95/99 (96%) |
| Event | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg |
|---|---|---|
| Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 9/131 | 12/99 |
| General physical health deteriorationGeneral disorders | 10/131 | 3/99 |
| PneumoniaInfections and infestations | 7/131 | 0/99 |
| VomitingGastrointestinal disorders | 2/131 | 5/99 |
| ConvulsionNervous system disorders | 6/131 | 5/99 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 4/131 | 5/99 |
| ThrombocytopeniaBlood and lymphatic system disorders | 6/131 | 2/99 |
| NauseaGastrointestinal disorders | 1/131 | 4/99 |
| HeadacheNervous system disorders | 4/131 | 4/99 |
| Intracranial pressure increasedNervous system disorders | 4/131 | 4/99 |
| Event | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg |
|---|---|---|
| NauseaGastrointestinal disorders | 49/131 | 37/99 |
| FatigueGeneral disorders | 40/131 | 37/99 |
| VomitingGastrointestinal disorders | 40/131 | 22/99 |
| HeadacheNervous system disorders | 33/131 | 20/99 |
| Oedema peripheralGeneral disorders | 31/131 | 24/99 |
| DiarrhoeaGastrointestinal disorders | 27/131 | 16/99 |
| ConstipationGastrointestinal disorders | 22/131 | 9/99 |
| DizzinessNervous system disorders | 13/131 | 15/99 |
| AnaemiaBlood and lymphatic system disorders | 19/131 | 10/99 |
| ThrombocytopeniaBlood and lymphatic system disorders | 19/131 | 10/99 |
| Age Continuous(years) | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg | Total |
|---|---|---|---|
| Mean | 53.7 ± 11.9 | 52.8 ± 11.4 | 53.3 ± 11.7 |
| Sex: Female, Male(Participants) | Imatinib 600 mg + Hydroxyurea 1000 mg | Imatinib 1000 mg + Hydroxyurea 1000 mg | Total |
|---|---|---|---|
| Female | 52 | 35 | 87 |
| Male | 79 | 65 | 144 |
The record gives a start of Feb 2006, a primary completion of Aug 2008 and a completion of Aug 2008. It does not say whether these dates are actual or estimated.
Results were first posted in May 2011, 2 years 9 months after primary completion.
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This study is terminated, as verified in Apr 2011. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Imatinib · Hydroxyurea