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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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00112502
First received: June 2, 2005
Last updated: September 23, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: Celecoxib
Drug: Isotretinoin
Drug: Temozolomide
Drug: Thalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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.


Enrollment: 178
Study Start Date: September 2005
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I: TMZ
Oral Temozolomide (TMZ) 150 mg/m^2 once daily on days 1-7 and 15-21.
Drug: Temozolomide
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
Other Name: Temodar
Experimental: Arm II: TMZ + Thalidomide
Temozolomide as in arm I and oral Thalidomide (Thal) once daily on days 1-28 (starting dose 200 mg).
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
Experimental: Arm III: TMZ + Isotretinoin
Temozolomide as in Arm I and oral Isotretinoin 40 mg/m^2 twice daily on days 1-21.
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
Experimental: Arm IV: TMZ + Celecoxib
Temozolomide as in arm I and oral Celecoxib 400 mg twice daily on days 1-28.
Drug: Celecoxib
400 mg orally twice a day continuous dosing
Other Name: Celebrex
Drug: Temozolomide
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
Other Name: Temodar
Experimental: Arm V: TMZ + Thalidomide + Isotretinoin
Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III.
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
Experimental: Arm VI: TMZ + Thalidomide + Celecoxib
Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV.
Drug: Celecoxib
400 mg orally twice a day continuous dosing
Other Name: Celebrex
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
Experimental: Arm VII: TMZ + Isotretinoin + Celecoxib
Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.
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
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.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112502

Locations
United States, Arkansas
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
Fort Smith, Arkansas, United States, 72913
United States, Florida
University of Texas MD Anderson Cancer Center at Orlando
Orlando, Florida, United States, 32806-2134
United States, Georgia
CCOP - Atlanta Regional
Atlanta, Georgia, United States, 30342-1701
United States, Illinois
CCOP - Central Illinois
Decatur, Illinois, United States, 62526
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
United States, Michigan
CCOP - Grand Rapids
Grand Rapids, Michigan, United States, 49503
CCOP - Kalamazoo
Kalamazoo, Michigan, United States, 49007-3731
United States, Missouri
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
Cancer Research for the Ozarks
Springfield, Missouri, United States, 65804
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210-1240
United States, South Carolina
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Marta Penas-Prado, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00112502     History of Changes
Other Study ID Numbers: 2004-0662, MDA-ID-02586, NCI-6636, MDA-2004-0662, CDR0000432954, NCI-2009-00076
Study First Received: June 2, 2005
Last Updated: September 23, 2014
Health Authority: United States: Federal Government

Keywords provided by M.D. Anderson Cancer Center:
adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Glioblastoma
Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Celecoxib
Dacarbazine
Isotretinoin
Temozolomide
Thalidomide
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on November 20, 2014