Clinical Trial Finder

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

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.

Arms

Active Comparator: Arm I: TMZ

Oral Temozolomide (TMZ) 150 mg/m^2 once daily on days 1-7 and 15-21.

Experimental: Arm II: TMZ + Thalidomide

Temozolomide as in arm I and oral Thalidomide (Thal) once daily on days 1-28 (starting dose 200 mg).

Experimental: Arm III: TMZ + Isotretinoin

Temozolomide as in Arm I and oral Isotretinoin 40 mg/m^2 twice daily on days 1-21.

Experimental: Arm IV: TMZ + Celecoxib

Temozolomide as in arm I and oral Celecoxib 400 mg twice daily on days 1-28.

Experimental: Arm V: TMZ + Thalidomide + Isotretinoin

Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III.

Experimental: Arm VI: TMZ + Thalidomide + Celecoxib

Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV.

Experimental: Arm VII: TMZ + Isotretinoin + Celecoxib

Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.

Experimental: 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.

Interventions

Drug: - Celecoxib

400 mg orally twice a day continuous dosing

Drug: - Isotretinoin

40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle.

Drug: - Temozolomide

150 mg/m2 orally daily, 7 days on treatment, 7 days off.

Drug: - Thalidomide

400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved)