A Randomized, Factorial-Design, Phase II Trial of Temozolomide Alone and in Combination With Possible Permutations of Thalidomide, Isotretinoin and/or Celecoxib as Post-Radiation Adjuvant Therapy of Glioblastoma Multiforme
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 178
- 试验地点
- 12
- 主要终点
- Median Progression-Free Survival (PFS) Comparison of Thalidomide Arms Versus no Thalidomide Arms
研究概览
简要总结
RATIONALE: 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. Thalidomide may stop the growth of glioblastoma multiforme by blocking blood flow to the tumor. Isotretinoin may help cells that are involved in the body's immune response to work better. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known which temozolomide-containing regimen is more effective in treating glioblastoma multiforme.
PURPOSE: This randomized phase II trial is studying eight different temozolomide-containing regimens to compare how well they work in treating patients who have undergone radiation therapy for glioblastoma multiforme.
详细描述
OBJECTIVES:
- Compare the efficacy of adjuvant temozolomide (TMZ) alone or in combination with thalidomide and/or isotretinoin and/or celecoxib, in terms of 6-month progression-free survival, in patients who have undergone radiotherapy for supratentorial glioblastoma multiforme.
- Compare the toxicity of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 8 treatment arms.
- Arm I: Patients receive oral temozolomide once daily on days 1-7 and 15-21.
- Arm II: Patients receive temozolomide as in arm I and oral thalidomide once daily on days 1-28.
- Arm III: Patients receive temozolomide as in arm I and oral isotretinoin twice daily on days 1-21.
- Arm IV: Patients receive temozolomide as in arm I and oral celecoxib twice daily on days 1-28.
- Arm V: Patients receive temozolomide as in arm I, thalidomide as in arm II, and isotretinoin as in arm III.
- Arm VI: Patients receive temozolomide as in arm I, thalidomide as in arm II, and celecoxib as in arm IV.
- Arm VII: Patients receive temozolomide as in arm I, isotretinoin as in arm III, and celecoxib as in arm IV.
- Arm VIII: Patients receive temozolomide as in arm I, thalidomide as in arm II, isotretinoin as in arm III, and celecoxib as in arm IV.
In all arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patient may receive additional courses of therapy at the discretion of the treating physician.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- 未提供
研究组 & 干预措施
Arm VI: TMZ + Thalidomide + Celecoxib
Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV.
干预措施: Celecoxib (Drug)
Arm I: TMZ
Oral Temozolomide (TMZ) 150 mg/m^2 once daily on days 1-7 and 15-21.
干预措施: Temozolomide (Drug)
Arm II: TMZ + Thalidomide
Temozolomide as in arm I and oral Thalidomide (Thal) once daily on days 1-28 (starting dose 200 mg).
干预措施: Temozolomide (Drug)
Arm II: TMZ + Thalidomide
Temozolomide as in arm I and oral Thalidomide (Thal) once daily on days 1-28 (starting dose 200 mg).
干预措施: Thalidomide (Drug)
Arm III: TMZ + Isotretinoin
Temozolomide as in Arm I and oral Isotretinoin 40 mg/m^2 twice daily on days 1-21.
干预措施: Isotretinoin (Drug)
Arm III: TMZ + Isotretinoin
Temozolomide as in Arm I and oral Isotretinoin 40 mg/m^2 twice daily on days 1-21.
干预措施: Temozolomide (Drug)
Arm IV: TMZ + Celecoxib
Temozolomide as in arm I and oral Celecoxib 400 mg twice daily on days 1-28.
干预措施: Celecoxib (Drug)
Arm IV: TMZ + Celecoxib
Temozolomide as in arm I and oral Celecoxib 400 mg twice daily on days 1-28.
干预措施: Temozolomide (Drug)
Arm V: TMZ + Thalidomide + Isotretinoin
Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III.
干预措施: Isotretinoin (Drug)
Arm V: TMZ + Thalidomide + Isotretinoin
Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III.
干预措施: Temozolomide (Drug)
Arm V: TMZ + Thalidomide + Isotretinoin
Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III.
干预措施: Thalidomide (Drug)
Arm VI: TMZ + Thalidomide + Celecoxib
Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV.
干预措施: Temozolomide (Drug)
Arm VI: TMZ + Thalidomide + Celecoxib
Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV.
干预措施: Thalidomide (Drug)
Arm VII: TMZ + Isotretinoin + Celecoxib
Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.
干预措施: Celecoxib (Drug)
Arm VII: TMZ + Isotretinoin + Celecoxib
Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.
干预措施: Isotretinoin (Drug)
Arm VII: TMZ + Isotretinoin + Celecoxib
Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.
干预措施: Temozolomide (Drug)
Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib
Temozolomide as in Arm I, Thalidomide as in Arm II, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.
干预措施: Celecoxib (Drug)
Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib
Temozolomide as in Arm I, Thalidomide as in Arm II, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.
干预措施: Isotretinoin (Drug)
Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib
Temozolomide as in Arm I, Thalidomide as in Arm II, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.
干预措施: Temozolomide (Drug)
Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib
Temozolomide as in Arm I, Thalidomide as in Arm II, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.
干预措施: Thalidomide (Drug)
结局指标
主要结局
Median Progression-Free Survival (PFS) Comparison of Thalidomide Arms Versus no Thalidomide Arms
时间窗: Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up, up to one year (12 study cycles).
Thalidomide versus not Thalidomide analysis: Comparison of median PFS outcome of participants in arms II, VI, VII and VIII, versus participants in arms I, III, IV and V. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Median Progression-Free Survival (PFS) Comparison of Celecoxib Arms Versus no Celecoxib Arms
时间窗: Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.
Celecoxib versus not Celecoxib analysis: We compared the median PFS outcome of participants in arms III, V, VI and VIII, versus participants in arms I, II, IV and VII. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Median Progression-Free Survival (PFS) Comparison of Isotretinoin Arms Versus no Isotretinoin Arms
时间窗: Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.
Isotretinoin versus not Isotretinoin analysis: We compared the median PFS outcome of participants in arms IV, V, VII and VIII, versus participants in arms I, II, III and VI. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
次要结局
- Median Overall Survival (OS) Comparison of Celecoxib Arms Versus no Celecoxib Arms(Every 3 months from randomization until progression of disease, death or last follow-up.)
- Median Progression-Free Survival (PFS) Comparison of Doublet Versus Triplet Therapy(Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.)
- Median Progression-Free Survival (PFS) of Individual Arms(Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.)
- Median Overall Survival (OS) Comparison of Isotretinoin Arms Versus no Isotretinoin Arms(Every 3 months from randomization until progression of disease, death or last follow-up.)
- Overall Survival of Individual Arms(Every 3 months from randomization until progression of disease, death or last follow-up.)
- Median Overall Survival (OS) Comparison of Thalidomide Arms Versus no Thalidomide Arms(Every 3 months from randomization until progression of disease, death or last follow-up.)
- Median Overall Survival (OS) Comparison of Doublet Versus Triplet Therapy(Every 3 months from randomization until progression of disease, death or last follow-up.)