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

NCT ID: NCT00112502

Last Updated: 2021-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2014-09-30

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.

Conditions

Brain and Central Nervous System Tumors; Glioblastoma Multiforme

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm I: TMZ

Oral Temozolomide (TMZ) 150 mg/m\^2 once daily on days 1-7 and 15-21.

Group Type: ACTIVE_COMPARATOR

Temozolomide

Intervention Type: DRUG

150 mg/m2 orally daily, 7 days on treatment, 7 days off.

Arm II: TMZ + Thalidomide

Temozolomide as in arm I and oral Thalidomide (Thal) once daily on days 1-28 (starting dose 200 mg).

Group Type: EXPERIMENTAL

Temozolomide

Intervention Type: DRUG

150 mg/m2 orally daily, 7 days on treatment, 7 days off.

Thalidomide

Intervention Type: DRUG

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)

Arm III: TMZ + Isotretinoin

Temozolomide as in Arm I and oral Isotretinoin 40 mg/m\^2 twice daily on days 1-21.

Group Type: EXPERIMENTAL

Isotretinoin

Intervention Type: DRUG

40 mg/m\^2 orally twice a day (total daily dose = 80 mg/m\^2) days 1-21 of a 28 day cycle.

Temozolomide

Intervention Type: DRUG

150 mg/m2 orally daily, 7 days on treatment, 7 days off.

Arm IV: TMZ + Celecoxib

Temozolomide as in arm I and oral Celecoxib 400 mg twice daily on days 1-28.

Group Type: EXPERIMENTAL

Celecoxib

Intervention Type: DRUG

400 mg orally twice a day continuous dosing

Temozolomide

Intervention Type: DRUG

150 mg/m2 orally daily, 7 days on treatment, 7 days off.

Arm V: TMZ + Thalidomide + Isotretinoin

Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III.

Group Type: EXPERIMENTAL

Isotretinoin

Intervention Type: DRUG

40 mg/m\^2 orally twice a day (total daily dose = 80 mg/m\^2) days 1-21 of a 28 day cycle.

Temozolomide

Intervention Type: DRUG

150 mg/m2 orally daily, 7 days on treatment, 7 days off.

Thalidomide

Intervention Type: DRUG

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)

Arm VI: TMZ + Thalidomide + Celecoxib

Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV.

Group Type: EXPERIMENTAL

Celecoxib

Intervention Type: DRUG

400 mg orally twice a day continuous dosing

Temozolomide

Intervention Type: DRUG

150 mg/m2 orally daily, 7 days on treatment, 7 days off.

Thalidomide

Intervention Type: DRUG

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)

Arm VII: TMZ + Isotretinoin + Celecoxib

Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV.

Group Type: EXPERIMENTAL

Celecoxib

Intervention Type: DRUG

400 mg orally twice a day continuous dosing

Isotretinoin

Intervention Type: DRUG

40 mg/m\^2 orally twice a day (total daily dose = 80 mg/m\^2) days 1-21 of a 28 day cycle.

Temozolomide

Intervention Type: DRUG

150 mg/m2 orally daily, 7 days on treatment, 7 days off.

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.

Group Type: EXPERIMENTAL

Celecoxib

Intervention Type: DRUG

400 mg orally twice a day continuous dosing

Isotretinoin

Intervention Type: DRUG

40 mg/m\^2 orally twice a day (total daily dose = 80 mg/m\^2) days 1-21 of a 28 day cycle.

Temozolomide

Intervention Type: DRUG

150 mg/m2 orally daily, 7 days on treatment, 7 days off.

Thalidomide

Intervention Type: DRUG

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)

Interventions

Celecoxib

400 mg orally twice a day continuous dosing

Intervention Type: 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.

Intervention Type: DRUG

Temozolomide

150 mg/m2 orally daily, 7 days on treatment, 7 days off.

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Celebrex; Accutane; 13-Cis-Retinoic Acid; Temodar; Thalomid

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marta Penas-Prado, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

Fort Smith, Arkansas, United States

University of Texas MD Anderson Cancer Center at Orlando

Orlando, Florida, United States

CCOP - Atlanta Regional

Atlanta, Georgia, United States

CCOP - Central Illinois

Decatur, Illinois, United States

CCOP - Wichita

Wichita, Kansas, United States

CCOP - Grand Rapids

Grand Rapids, Michigan, United States

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

CCOP - Kansas City

Kansas City, Missouri, United States

Cancer Research for the Ozarks

Springfield, Missouri, United States

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

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. doi: 10.1093/neuonc/noq100. Epub 2010 Aug 20.

Reference Type: RESULT

PMID: 20729242 (View on PubMed)

Penas-Prado M, Hess KR, Fisch MJ, Lagrone LW, Groves MD, Levin VA, De Groot JF, Puduvalli VK, Colman H, Volas-Redd G, Giglio P, Conrad CA, Salacz ME, Floyd JD, Loghin ME, Hsu SH, Gonzalez J, Chang EL, Woo SY, Mahajan A, Aldape KD, Yung WK, Gilbert MR; MD Anderson Community Clinical Oncology Program; Brain Tumor Trials Collaborative. Randomized phase II adjuvant factorial study of dose-dense temozolomide alone and in combination with isotretinoin, celecoxib, and/or thalidomide for glioblastoma. Neuro Oncol. 2015 Feb;17(2):266-73. doi: 10.1093/neuonc/nou155. Epub 2014 Sep 19.

Reference Type: DERIVED

PMID: 25239666 (View on PubMed)

Related Links

http://www.mdanderson.org

University of Texas (UT) MD Anderson Cancer Center Official Website

Other Identifiers

MDA-ID-02586

Identifier Type: -

Identifier Source: secondary_id

NCI-6636

Identifier Type: -

Identifier Source: secondary_id

MDA-2004-0662

Identifier Type: -

Identifier Source: secondary_id

CDR0000432954

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-00076

Identifier Type: REGISTRY

Identifier Source: secondary_id

2004-0662

Identifier Type: -

Identifier Source: org_study_id