Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme

M.D. Anderson Cancer Center

Status and phase: Completed; Phase 2

Conditions: Glioblastoma Multiforme; Brain and Central Nervous System Tumors

Treatments: Drug: Temozolomide; Drug: Celecoxib; Drug: Thalidomide; Drug: Isotretinoin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00112502

NCI-6636

MDA-2004-0662

MDA-ID-02586

NCI-2009-00076 (Registry Identifier)

2004-0662

CDR0000432954 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 178 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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178 participants in 8 patient groups

Arm I: TMZ

Active Comparator group

Description:

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

Treatment:

Drug: Temozolomide

Arm II: TMZ + Thalidomide

Experimental group

Description:

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

Treatment:

Drug: Thalidomide

Drug: Temozolomide

Arm III: TMZ + Isotretinoin

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Isotretinoin

Arm IV: TMZ + Celecoxib

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Celecoxib

Arm V: TMZ + Thalidomide + Isotretinoin

Experimental group

Description:

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

Treatment:

Drug: Thalidomide

Drug: Temozolomide

Drug: Isotretinoin

Arm VI: TMZ + Thalidomide + Celecoxib

Experimental group

Description:

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

Treatment:

Drug: Thalidomide

Drug: Temozolomide

Drug: Celecoxib

Arm VII: TMZ + Isotretinoin + Celecoxib

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Celecoxib

Drug: Isotretinoin

Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib

Experimental group

Description:

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

Treatment:

Drug: Thalidomide

Drug: Temozolomide

Drug: Celecoxib

Drug: Isotretinoin