Official Title: “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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

Study Primary Completion Date: December 2006

OBJECTIVES: - Compare the efficacy of adjuvant temozolomide 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 176 patients (22 per treatment arm) will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: celecoxib
  • Given orally
• Drug: isotretinoin
  • Given orally
• Drug: temozolomide
  • Given orally
• Drug: thalidomide
  • Given orally

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Arm I
  • Patients receive oral temozolomide once daily on days 1-7 and 15-21.
• Experimental: Arm II
  • Patients receive temozolomide as in arm I and oral thalidomide once daily on days 1-28.
• Experimental: Arm III
  • Patients receive temozolomide as in arm I and oral isotretinoin twice daily on days 1-21.
• Experimental: Arm IV
  • Patients receive temozolomide as in arm I and oral celecoxib twice daily on days 1-28.
• Experimental: Arm V
  • Patients receive temozolomide as in arm I, thalidomide as in arm II, and isotretinoin as in arm III.
• Experimental: Arm VI
  • Patients receive temozolomide as in arm I, thalidomide as in arm II, and celecoxib as in arm IV.
• Experimental: Arm VII
  • Patients receive temozolomide as in arm I, isotretinoin as in arm III, and celecoxib as in arm IV.
• Experimental: 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.

Primary Measures

• Progression-free survival at 6 months
  • Safety Issue?: No
• Toxicity
  • Safety Issue?: Yes

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
• SGPT < 2 times upper limit of normal (ULN)
• Alkaline phosphatase < 2 times ULN
• Bilirubin ≤ 1.5 mg/dL
• Renal
• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: M.D. Anderson Cancer Center

Overall Clinical Trial Officials and Contacts

Mark R. Gilbert, MD Study Chair M.D. Anderson Cancer Center  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00112502

Study ID Number: CDR0000432954

ClinicalTrials.gov Identifier: NCT00112502

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database