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:	Treatment, Randomized, Active Control
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:	176
Study Start Date:	September 2005
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator Patients receive oral temozolomide once daily on days 1-7 and 15-21.	Drug: temozolomide Given orally
Arm II: Experimental Patients receive temozolomide as in arm I and oral thalidomide once daily on days 1-28.	Drug: temozolomide Given orally Drug: thalidomide Given orally
Arm III: Experimental Patients receive temozolomide as in arm I and oral isotretinoin twice daily on days 1-21.	Drug: isotretinoin Given orally Drug: temozolomide Given orally
Arm IV: Experimental Patients receive temozolomide as in arm I and oral celecoxib twice daily on days 1-28.	Drug: celecoxib Given orally Drug: temozolomide Given orally
Arm V: Experimental 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
Arm VI: Experimental 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
Arm VII: Experimental 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
Arm VIII: Experimental 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 176 patients (22 per treatment arm) 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	Recruiting
Fort Smith, Arkansas, United States, 72913
Contact: Tony A. Flippin, MD 479-484-4700 tflippin@cooperclinic.com
United States, Florida
M.D. Anderson Cancer Center at Orlando	Recruiting
Orlando, Florida, United States, 32806-2134
Contact: Jennifer Tseng, MD 407-648-3800 ext. 8553 jtseng@mdanderson.org
United States, Georgia
CCOP - Atlanta Regional	Recruiting
Atlanta, Georgia, United States, 30342-1701
Contact: Thomas E. Seay, MD, PhD 404-851-7115
United States, Illinois
CCOP - Central Illinois	Recruiting
Decatur, Illinois, United States, 62526
Contact: James L. Wade, MD 217-876-6600 jlwade3@sbcglobal.net
United States, Kansas
CCOP - Wichita	Recruiting
Wichita, Kansas, United States, 67214-3882
Contact: Shaker R. Dakhil, MD, FACP 316-268-5784
United States, Michigan
CCOP - Grand Rapids	Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Marianne K. Lange, MD 616-391-1230 marianne.lange@grcop.org
CCOP - Kalamazoo	Recruiting
Kalamazoo, Michigan, United States, 49007-3731
Contact: Raymond S. Lord, MD 269-373-7458 rlord@wmcc.org
United States, Missouri
Cancer Research for the Ozarks	Recruiting
Springfield, Missouri, United States, 65804
Contact: John W. Goodwin, MD 417-889-8099 jgoodwin@sprg.mercy.net
CCOP - Kansas City	Recruiting
Kansas City, Missouri, United States, 64131
Contact: Rakesh Gaur, MD 816-823-0555 rgaur@saint-lukes.org
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Herbert B. Newton, MD 866-627-7616 osu@emergingmed.com
United States, South Carolina
CCOP - Upstate Carolina	Recruiting
Spartanburg, South Carolina, United States, 29303
Contact: James D. Bearden, MD 864-560-6812 jbearde@srhs.com
United States, Texas
M. D. Anderson Cancer Center at University of Texas	Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U 713-792-3245

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

No publications provided

Responsible Party:	University of Texas M.D. Anderson CCOP Research Base ( Michael J. Fisch )
Study ID Numbers:	CDR0000432954, MDA-ID-02586, NCI-6636, MDA-2004-0662
Study First Received:	June 2, 2005
Last Updated:	September 22, 2009
ClinicalTrials.gov Identifier:	NCT00112502 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Anti-Infective Agents
Glioblastoma
Molecular Mechanisms of Pharmacological Action
Thalidomide
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Central Nervous System Neoplasms
Anti-Bacterial Agents
Neoplasms by Site
Sensory System Agents
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses

Isotretinoin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Growth Inhibitors
Angiogenesis Modulating Agents
Glioma
Alkylating Agents
Dermatologic Agents
Nervous System Neoplasms
Neoplasms by Histologic Type
Celecoxib
Astrocytoma
Growth Substances
Cyclooxygenase Inhibitors
Nervous System Diseases

ClinicalTrials.gov processed this record on November 09, 2009