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)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Novartis
- 入组人数
- 231
- 试验地点
- 1
- 主要终点
- Percentage of Patients With an Objective Overall Response (OOR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •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.
- •Patients who had undergone major surgery within 2 weeks prior to study entry or who had not recovered from prior major surgery, patients who had received chemotherapy within 4 weeks prior to study start, or who have not recovered from toxic effects of such therapy.
- •Impairment of gastrointestinal function or gastrointestinal disease that could significantly alter the absorption of imatinib.
- •Patients taking warfarin sodium.
- •Known history of human immunodeficiency virus (HIV) seropositivity; testing for HIV was not required at study entry.
- •For the purposes of MRI, patients with a pacemaker, ferromagnetic metal implants other than those approved as safe for use in MR scanners (eg, some types of aneurysm clips, shrapnel), patients suffering from uncontrollable claustrophobia, or those physically unable to fit into the machine (eg, obesity).
- •Patients considered by the investigator as unlikely to be compliant with the study, take the study medications, travel for the necessary assessment visits, or have other medical conditions likely to interfere with the study assessments.
- •Patients with another primary malignancy treated within the prior 3 years except excised squamous cell carcinomas of the skin and carcinoma in situ lesions of other organs which had been treated for cure.
- •Patients not able to provide reliable informed consent and who did not have a legal representative for healthcare decisions on their behalf.
研究组 & 干预措施
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.
干预措施: Imatinib tablets (Drug)
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.
干预措施: Hydroxyurea capsules (Drug)
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.
干预措施: Imatinib tablets (Drug)
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.
干预措施: Hydroxyurea capsules (Drug)
结局指标
主要结局
Percentage of Patients With an Objective Overall Response (OOR)
时间窗: 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).
次要结局
- 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))