Phase III Trial Comparing Conventional Adjuvant Temozolomide With Dose-Intensive Temozolomide in Patients With Newly Diagnosed Glioblastoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,173
- 试验地点
- 347
- 主要终点
- Median Overall Survival Time
研究概览
简要总结
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide may kill more tumor cells. It is not yet known which schedule of temozolomide when given together with radiation therapy is more effective in treating glioblastoma or gliosarcoma.
PURPOSE: This randomized phase III trial is studying two different schedules of temozolomide to compare how well they work when given together with radiation therapy in treating patients with newly diagnosed glioblastoma or gliosarcoma.
详细描述
OBJECTIVES:
Primary
- Determine if dose-intensifying (increasing the "dose-density") the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy as measured by overall survival of patients with newly diagnosed glioblastoma or gliosarcoma.
Secondary
- Determine if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy as measured by progression-free survival.
- Determine in patients with unmethylated MGMT (O-6-methylguanine-DNA methyltransferase) if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy (overall and progression-free survival) compared with patients receiving conventional temozolomide dosing.
- Determine in patients with methylated MGMT if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy (overall and progression-free survival) compared with patients receiving conventional temozolomide dosing.
- Determine if there is an association between tumor MGMT gene methylation status and treatment response.
- Compare and record the toxicities of the conventional and dose-intense chemotherapy regimens.
- Evaluate whether 6-month progression-free survival is associated with overall survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 120 Years（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
- 未提供
研究组 & 干预措施
Conventional adjuvant TMZ
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
干预措施: Concurrent temozolomide (Drug)
Conventional adjuvant TMZ
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
干预措施: Concurrent radiation therapy (Radiation)
Conventional adjuvant TMZ
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
干预措施: 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle (Drug)
Dose-dense adjuvant TMZ
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
干预措施: Concurrent temozolomide (Drug)
Dose-dense adjuvant TMZ
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
干预措施: Concurrent radiation therapy (Radiation)
Dose-dense adjuvant TMZ
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
干预措施: 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle (Drug)
No adjuvant TMZ (not randomized )
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm.
干预措施: Concurrent temozolomide (Drug)
No adjuvant TMZ (not randomized )
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm.
干预措施: Concurrent radiation therapy (Radiation)
结局指标
主要结局
Median Overall Survival Time
时间窗: From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Analysis occurred after 647 deaths were reported.
次要结局
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 4(baseline and cycle 4 (approximately 22 weeks))
- Mean MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score Over Time(Baseline, 10, 12, 22, 24, and 46 weeks)
- Determination of Impactful Baseline Instruments on Overall Survival(From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.)
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition (DR) Score at Cycle 4(baseline and cycle 4 (approximately 22 weeks))
- Median Progression-free Survival (PFS) Time(From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.)
- Median Overall Survival Time by MGMT Status(From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.)
- Median Progression-free Survival Time by MGMT Status(From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.)
- Best Treatment Response by MGMT Status(From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.)
- Distribution of Highest Grade AE Reported as Possibly/Probably/Definitely Related to Protocol Treatment(From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.)
- Overall Survival Status by Progression Status at 6 Months(From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.)
- Mean MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy(Baseline and cycle 10 (approximately 46 weeks))
- Mean Neurocognitive Function (NCF) Composite Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy(Baseline and cycle 10 (approximately 46 weeks))
- Mean EORTC QLQ-C30 Global Health Status Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy(Baseline and cycle 10 (approximately 46 weeks))
- Mean Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Mid-cyle for Cycle 1(Baseline and mid-cycle 1 (approximately 12 weeks))
- Mean Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Mid-cyle for Cycle 4(Baseline and mid-cycle 4 (approximately 24 weeks))
- Mean Change From Baseline in EORTC QLQ-C30 Global Health Status Score at Mid-cyle for Cycle 1(Baseline and mid-cycle 1 (approximately 12 weeks))
- Mean Change From Baseline in EORTC QLQ-C30 Global Health Status Score at Mid-cyle for Cycle 4(Baseline and mid-cycle 4 (approximately 24 weeks))
- Change From Baseline in Mean EORTC QLQ-C30 Global Health Status(Baseline, 10,12, 22, 24, and 46 weeks)
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Cycle 4(baseline and cycle 4 (approximately 22 weeks))
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Interference Score at Cycle 4(baseline and cycle 4 (approximately 22 weeks))
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 10(baseline and cycle 10 (approximately 46 weeks))
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 1(baseline and cycle 1 (approximately 10 weeks))
- Mean Neurocognitive Function (NCF) Composite Score Over Time(Baseline, 10, 22, and 46 weeks)
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition Score at Cycle 1(baseline and cycle 1 (approximately 10 weeks))
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition (DR) Score at Cycle 10(baseline and cycle 10 (approximately 46 weeks))