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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00112502
First received: June 2, 2005
Last updated: November 14, 2013
Last verified: November 2013

June 2, 2005
November 14, 2013
September 2005
May 2015   (final data collection date for primary outcome measure)
Progression-free survival at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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.
Not Provided
Complete list of historical versions of study NCT00112502 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
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Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
  • Drug: Celecoxib
    400 mg orally twice a day continuous dosing
    Other Name: Celebrex
  • 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.
    Other Names:
    • Accutane
    • 13-Cis-Retinoic Acid
  • Drug: Temozolomide
    150 mg/m2 orally daily, 7 days on treatment, 7 days off.
    Other Name: Temodar
  • 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)
    Other Name: Thalomid
  • Active Comparator: Arm I: TMZ
    Oral Temozolomide (TMZ) 150 mg/m^2 once daily on days 1-7 and 15-21.
    Intervention: Drug: Temozolomide
  • Experimental: Arm II: TMZ + Thalidomide
    Temozolomide as in arm I and oral Thalidomide (Thal) once daily on days 1-28 (starting dose 200 mg).
    Interventions:
    • Drug: Temozolomide
    • Drug: Thalidomide
  • Experimental: Arm III: TMZ + Isotretinoin
    Temozolomide as in Arm I and oral Isotretinoin 40 mg/m^2 twice daily on days 1-21.
    Interventions:
    • Drug: Isotretinoin
    • Drug: Temozolomide
  • Experimental: Arm IV: TMZ + Celecoxib
    Temozolomide as in arm I and oral Celecoxib 400 mg twice daily on days 1-28.
    Interventions:
    • Drug: Celecoxib
    • Drug: Temozolomide
  • Experimental: Arm V: TMZ + Thalidomide + Isotretinoin
    Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III.
    Interventions:
    • Drug: Isotretinoin
    • Drug: Temozolomide
    • Drug: Thalidomide
  • Experimental: Arm VI: TMZ + Thalidomide + Celecoxib
    Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV.
    Interventions:
    • Drug: Celecoxib
    • Drug: Temozolomide
    • Drug: Thalidomide
  • Experimental: Arm VII: TMZ + Isotretinoin + Celecoxib
    Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.
    Interventions:
    • Drug: Celecoxib
    • Drug: Isotretinoin
    • Drug: Temozolomide
  • 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
    • Drug: Isotretinoin
    • Drug: Temozolomide
    • Drug: Thalidomide
Gilbert MR, Gonzalez J, Hunter K, Hess K, Giglio P, Chang E, Puduvalli V, Groves MD, Colman H, Conrad C, Levin V, Woo S, Mahajan A, de Groot J, Yung WK. A phase I factorial design study of dose-dense temozolomide alone and in combination with thalidomide, isotretinoin, and/or celecoxib as postchemoradiation adjuvant therapy for newly diagnosed glioblastoma. Neuro Oncol. 2010 Nov;12(11):1167-72. Epub 2010 Aug 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
180
Not Provided
May 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00112502
2004-0662, MDA-ID-02586, NCI-6636, MDA-2004-0662, CDR0000432954
No
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study Chair: Mark R. Gilbert, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP