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
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
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
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed supratentorial glioblastoma multiforme
- Must have undergone a biopsy OR subtotal or gross total resection of the tumor
- Must have completed post-operative (or post-biopsy) radiotherapy within the past 5
weeks
- No progressive disease after radiotherapy
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Karnofsky 60-100%
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Serum glutamate pyruvate transaminase (SGPT) < 2 times upper limit of normal (ULN)
- Alkaline phosphatase < 2 times ULN
- Bilirubin ≤ 1.5 mg/dL
Renal
- blood urea nitrogen (BUN) ≤ 1.5 times ULN
- Creatinine ≤ 1.5 times ULN
Immunologic
- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to celecoxib or to sulfonamides
- No asthma, urticaria, or allergic reactions to aspirin or other NSAIDs
- No active infection
Gastrointestinal
- No inflammatory bowel disease
- No history of peptic ulcer disease
- No gastrointestinal bleeding within past 3 months
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method contraception during and for 2
months after study participation
- Fertile female patients randomized to receive thalidomide must use effective
double-method contraception for ≥ 4 weeks before, during, and ≥ 4 weeks after
completion of study therapy
- Fertile male patients randomized to receive thalidomide must use effective
contraception during and for ≥ 4 weeks after completion of study therapy
- No blood donation (for patients randomized to receive thalidomide)
- No history of any other cancer except nonmelanoma skin cancer or carcinoma in situ of
the cervix or cancer that is in complete remission and patient completed all therapy
for that disease ≥ 3 years ago
- No other disease that would obscure toxicity or dangerously alter drug metabolism
(e.g., severe connective tissue disease)
- No other serious medical illness
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Prior temozolomide in combination with radiotherapy allowed
- No other prior or concurrent chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- See Disease Characteristics
- See Chemotherapy
Surgery
- See Disease Characteristics
- No concurrent surgery
Other
- No other concurrent non-steroidal anti-inflammatory drugs (NSAIDs) (for patients
randomized to receive celecoxib)
- No other concurrent investigational drugs
- No other concurrent anticancer therapy
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Outcome Measure:
Progression-free survival at 6 months
Outcome Description:
Number of participants with no disease progression, measured at 6 months. A combination of the neurological examination and MRI brain scan used to define progression.
Outcome Time Frame:
6 months
Safety Issue:
No
Principal Investigator
Mark R. Gilbert, MD
Investigator Role:
Study Chair
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Federal Government
Study ID:
2004-0662
NCT ID:
NCT00112502
Start Date:
September 2005
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- adult giant cell glioblastoma
- adult gliosarcoma
- adult glioblastoma
- Glioblastoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| CCOP - Upstate Carolina | Spartanburg, South Carolina 29303 |
| CCOP - Wichita | Wichita, Kansas 67214-3882 |
| CCOP - Atlanta Regional | Atlanta, Georgia 30342-1701 |
| CCOP - Kansas City | Kansas City, Missouri 64131 |
| CCOP - Kalamazoo | Kalamazoo, Michigan 49007-3731 |
| CCOP - Central Illinois | Springfield, Illinois 62526 |
| Cancer Research for the Ozarks | Springfield, Missouri 65807 |
| CCOP - Grand Rapids | Grand Rapids, Michigan 49503 |
| M.D. Anderson Cancer Center at Orlando | Orlando, Florida 32806 |
| M. D. Anderson Cancer Center at University of Texas | Houston, Texas 77030-4009 |
| Hembree Mercy Cancer Center at St. Edward Mercy Medical Center | Ft. Smith, Arkansas 72903 |
| Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center | Columbus, Ohio 43210-1240 |
