Clinical trial NCT00112502: Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Glioblastoma Multiforme
Keywords: adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-06-03
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Median Progression-Free Survival (PFS) Comparison of Thalidomide Arms Versus no Thalidomide Arms
timeFrame: Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up, up to one year (12 study cycles).
measure: Median Progression-Free Survival (PFS) Comparison of Celecoxib Arms Versus no Celecoxib Arms
timeFrame: Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.
measure: Median Progression-Free Survival (PFS) Comparison of Isotretinoin Arms Versus no Isotretinoin Arms
timeFrame: Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.
Secondary outcomes:
measure: Median Progression-Free Survival (PFS) Comparison of Doublet Versus Triplet Therapy
timeFrame: Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.
measure: Median Progression-Free Survival (PFS) of Individual Arms
timeFrame: Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.
measure: Median Overall Survival (OS) Comparison of Thalidomide Arms Versus no Thalidomide Arms
timeFrame: Every 3 months from randomization until progression of disease, death or last follow-up.
measure: Median Overall Survival (OS) Comparison of Celecoxib Arms Versus no Celecoxib Arms
timeFrame: Every 3 months from randomization until progression of disease, death or last follow-up.
measure: Median Overall Survival (OS) Comparison of Isotretinoin Arms Versus no Isotretinoin Arms
timeFrame: Every 3 months from randomization until progression of disease, death or last follow-up.
measure: Median Overall Survival (OS) Comparison of Doublet Versus Triplet Therapy
timeFrame: Every 3 months from randomization until progression of disease, death or last follow-up.
measure: Overall Survival of Individual Arms
timeFrame: Every 3 months from randomization until progression of disease, death or last follow-up.
Other outcomes:
Locations:
city: Fort Smith
country: United States
facility: Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
state: Arkansas
city: Orlando
country: United States
facility: University of Texas MD Anderson Cancer Center at Orlando
state: Florida
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
state: Georgia
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Springfield
country: United States
facility: Cancer Research for the Ozarks
state: Missouri
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
state: Ohio
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Marta Penas-Prado, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.