Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme
- Conditions
- Brain and Central Nervous System TumorsGlioblastoma Multiforme
- Interventions
- Registration Number
- NCT00112502
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
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.
- Detailed Description
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.
After completion of study treatment, patients are followed for at least 30 days and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 180 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 178
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Arm III: TMZ + Isotretinoin Temozolomide Temozolomide as in Arm I and oral Isotretinoin 40 mg/m\^2 twice daily on days 1-21. Arm IV: TMZ + Celecoxib Celecoxib Temozolomide as in arm I and oral Celecoxib 400 mg twice daily on days 1-28. Arm VI: TMZ + Thalidomide + Celecoxib Celecoxib Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV. Arm I: TMZ Temozolomide Oral Temozolomide (TMZ) 150 mg/m\^2 once daily on days 1-7 and 15-21. Arm II: TMZ + Thalidomide Temozolomide Temozolomide as in arm I and oral Thalidomide (Thal) once daily on days 1-28 (starting dose 200 mg). Arm II: TMZ + Thalidomide Thalidomide Temozolomide as in arm I and oral Thalidomide (Thal) once daily on days 1-28 (starting dose 200 mg). Arm III: TMZ + Isotretinoin Isotretinoin Temozolomide as in Arm I and oral Isotretinoin 40 mg/m\^2 twice daily on days 1-21. Arm V: TMZ + Thalidomide + Isotretinoin Isotretinoin Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III. Arm IV: TMZ + Celecoxib Temozolomide Temozolomide as in arm I and oral Celecoxib 400 mg twice daily on days 1-28. Arm V: TMZ + Thalidomide + Isotretinoin Thalidomide Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III. Arm V: TMZ + Thalidomide + Isotretinoin Temozolomide Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III. Arm VI: TMZ + Thalidomide + Celecoxib Thalidomide Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV. Arm VII: TMZ + Isotretinoin + Celecoxib Celecoxib Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV. Arm VI: TMZ + Thalidomide + Celecoxib Temozolomide Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV. Arm VII: TMZ + Isotretinoin + Celecoxib Temozolomide Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV. Arm VII: TMZ + Isotretinoin + Celecoxib Isotretinoin Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV. Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Celecoxib Temozolomide as in Arm I, Thalidomide as in Arm II, Isotretinoin as in Arm III, and Celecoxib as in Arm IV. Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Isotretinoin Temozolomide as in Arm I, Thalidomide as in Arm II, Isotretinoin as in Arm III, and Celecoxib as in Arm IV. Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Temozolomide Temozolomide as in Arm I, Thalidomide as in Arm II, Isotretinoin as in Arm III, and Celecoxib as in Arm IV. Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Thalidomide Temozolomide as in Arm I, Thalidomide as in Arm II, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.
- Primary Outcome Measures
Name Time Method Median Progression-Free Survival (PFS) Comparison of Thalidomide Arms Versus no Thalidomide Arms 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 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 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).
- Secondary Outcome Measures
Name Time Method 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. Celecoxib versus not Celecoxib analysis: We compared the median OS outcome of participants in arms III, V, VI and VIII, versus participants in arms I, II, IV and VII. Median OS 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 Doublet Versus Triplet Therapy Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up. Doublet (2 agents) versus Triplet (3 agents) therapy analysis: We compared the median PFS outcome of participants in arms II, III, IV, versus participants in arms V, VI 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) of Individual Arms Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up. 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 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. Isotretinoin versus not Isotretinoin analysis: We compared the median OS outcome of participants in arms IV, V, VII and VIII, versus participants in arms I, II, III and VI. Median OS 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).
Overall Survival of Individual Arms Every 3 months from randomization until progression of disease, death or last follow-up. Overall Survival (OS) 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 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. Thalidomide versus not Thalidomide analysis: We compared the median OS outcome of participants in arms II, VI, VII and VIII, versus participants in arms I, III, IV and V. Median OS 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 Overall Survival (OS) Comparison of Doublet Versus Triplet Therapy Every 3 months from randomization until progression of disease, death or last follow-up. Doublet (2 agents) versus Triplet (3 agents) therapy analysis: We compared the median OS outcome of participants in arms II, III, IV, versus participants in arms V, VI and VII. Median OS 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).
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Trial Locations
- Locations (12)
CCOP - Atlanta Regional
🇺🇸Atlanta, Georgia, United States
CCOP - Central Illinois
🇺🇸Decatur, Illinois, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
CCOP - Upstate Carolina
🇺🇸Spartanburg, South Carolina, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
CCOP - Wichita
🇺🇸Wichita, Kansas, United States
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
🇺🇸Fort Smith, Arkansas, United States
CCOP - Grand Rapids
🇺🇸Grand Rapids, Michigan, United States
CCOP - Kalamazoo
🇺🇸Kalamazoo, Michigan, United States
Cancer Research for the Ozarks
🇺🇸Springfield, Missouri, United States
University of Texas MD Anderson Cancer Center at Orlando
🇺🇸Orlando, Florida, United States
CCOP - Kansas City
🇺🇸Kansas City, Missouri, United States