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

Condition(s) targeted: Brain and Central Nervous System Tumors

Intervention: celecoxib (Drug); isotretinoin (Drug); temozolomide (Drug); thalidomide (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Mark R. Gilbert, MD, Study Chair, Affiliation: M.D. Anderson Cancer Center

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.

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

Study design: Treatment, Randomized, Active Control

Primary outcome:

Progression-free survival at 6 months

Toxicity

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center, Fort Smith, Arkansas 72913, United States; Recruiting
Tony A. Flippin, MD, Phone: 479-484-4700, Email: tflippin@cooperclinic.com

M.D. Anderson Cancer Center at Orlando, Orlando, Florida 32806-2134, United States; Recruiting
Jennifer Tseng, MD, Phone: 407-648-3800 ext. 8553, Email: jtseng@mdanderson.org

CCOP - Atlanta Regional, Atlanta, Georgia 30342-1701, United States; Recruiting
Thomas E. Seay, MD, PhD, Phone: 404-851-7115

CCOP - Central Illinois, Decatur, Illinois 62526, United States; Recruiting
James L. Wade, MD, Phone: 217-876-6600, Email: jlwade3@sbcglobal.net

CCOP - Wichita, Wichita, Kansas 67214-3882, United States; Recruiting
Shaker R. Dakhil, MD, FACP, Phone: 316-268-5784

CCOP - Grand Rapids, Grand Rapids, Michigan 49503, United States; Recruiting
Marianne K. Lange, MD, Phone: 616-391-1230, Email: marianne.lange@grcop.org

CCOP - Kalamazoo, Kalamazoo, Michigan 49007-3731, United States; Recruiting
Raymond S. Lord, MD, Phone: 269-373-7458, Email: rlord@wmcc.org

Cancer Research for the Ozarks, Springfield, Missouri 65804, United States; Recruiting
John W. Goodwin, MD, Phone: 417-889-8099, Email: jgoodwin@sprg.mercy.net

CCOP - Kansas City, Kansas City, Missouri 64131, United States; Recruiting
Rakesh Gaur, MD, Phone: 816-823-0555, Email: rgaur@saint-lukes.org

CCOP - Upstate Carolina, Spartanburg, South Carolina 29303, United States; Recruiting
James D. Bearden, MD, Phone: 864-560-6812, Email: jbearde@srhs.com

M. D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States; Recruiting
Clinical Trials Office - M. D. Anderson Cancer Center at the U, Phone: 713-792-3245

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: September 2005
Last updated: October 28, 2008