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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

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ClinicalTrials.gov Identifier: NCT00112502
Recruitment Status : Completed
First Posted : June 3, 2005
Last Update Posted : September 25, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE June 2, 2005
First Posted Date  ICMJE June 3, 2005
Last Update Posted Date September 25, 2014
Study Start Date  ICMJE September 2005
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2012)
Progression-free survival at 6 months [ Time Frame: 6 months ]
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00112502 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme
Official Title  ICMJE 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
Brief Summary

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.

Detailed 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.

Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE
  • 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
Study Arms
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 23, 2014)
178
Original Enrollment  ICMJE Not Provided
Study Completion Date Not Provided
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00112502
Other Study ID Numbers  ICMJE 2004-0662
MDA-ID-02586
NCI-6636
MDA-2004-0662
CDR0000432954 ( Other Identifier: NCI )
NCI-2009-00076 ( Registry Identifier: NCI CTRP )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Marta Penas-Prado, MD M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date September 2014

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