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

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00112502

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 II

Study Type:	Interventional
Study Design:	Allocation: Randomized 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:

MedlinePlus related topics: Cancer

Drug Information available for: Thalidomide Temozolomide Celecoxib Isotretinoin

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival at 6 months [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	180
Study Start Date:	September 2005
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

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

Detailed Description:

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 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

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

Contacts and Locations

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
M.D. 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
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Mark R. Gilbert, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Michael J. Fisch, University of Texas M.D. Anderson CCOP Research Base
ClinicalTrials.gov Identifier:	NCT00112502 History of Changes
Other Study ID Numbers:	CDR0000432954, MDA-ID-02586, NCI-6636, MDA-2004-0662
Study First Received:	June 2, 2005
Last Updated:	March 25, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma

Additional relevant MeSH terms:

Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Isotretinoin

Thalidomide
Temozolomide
Dacarbazine
Celecoxib
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on February 12, 2012