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

NCT00112502 | Completed Phase 2 Results

• 6 other identifiers: 2004-0662MDA-ID-02586NCI-6636MDA-2004-0662CDR0000432954NCI-2009-00076
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 12

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.

Conditions

Brain and Central Nervous System Tumors; Glioblastoma Multiforme

Keywords

adult giant cell glioblastoma; adult gliosarcoma; adult glioblastoma

Outcome Measures

Primary Outcomes (3)

• Median Progression-Free Survival (PFS) Comparison of Thalidomide Arms Versus no Thalidomide Arms

  Thalidomide versus not Thalidomide analysis: Comparison of median PFS outcome of participants in arms II, VI, VII and VIII, versus participants in arms I, III, IV and V. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

  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).

• Median Progression-Free Survival (PFS) Comparison of Celecoxib Arms Versus no Celecoxib Arms

  Celecoxib versus not Celecoxib analysis: We compared the median PFS outcome of participants in arms III, V, VI and VIII, versus participants in arms I, II, IV and VII. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

  Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.

• Median Progression-Free Survival (PFS) Comparison of Isotretinoin Arms Versus no Isotretinoin Arms

  Isotretinoin versus not Isotretinoin analysis: We compared the median PFS outcome of participants in arms IV, V, VII and VIII, versus participants in arms I, II, III and VI. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

  Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.

Secondary Outcomes (7)

• Median Progression-Free Survival (PFS) Comparison of Doublet Versus Triplet Therapy

  Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.

• Median Progression-Free Survival (PFS) of Individual Arms

  Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.

• Median Overall Survival (OS) Comparison of Thalidomide Arms Versus no Thalidomide Arms

  Every 3 months from randomization until progression of disease, death or last follow-up.

• Median Overall Survival (OS) Comparison of Celecoxib Arms Versus no Celecoxib Arms

  Every 3 months from randomization until progression of disease, death or last follow-up.

• Median Overall Survival (OS) Comparison of Isotretinoin Arms Versus no Isotretinoin Arms

  Every 3 months from randomization until progression of disease, death or last follow-up.

Study Arms (8)

Arm I: TMZ

ACTIVE COMPARATOR

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

Drug: Temozolomide

Arm II: TMZ + Thalidomide

EXPERIMENTAL

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

Drug: Temozolomide; Drug: Thalidomide

Arm III: TMZ + Isotretinoin

EXPERIMENTAL

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

Drug: Isotretinoin; Drug: Temozolomide

Arm IV: TMZ + Celecoxib

EXPERIMENTAL

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

Drug: Celecoxib; Drug: Temozolomide

Arm V: TMZ + Thalidomide + Isotretinoin

EXPERIMENTAL

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

Drug: Isotretinoin; Drug: Temozolomide; Drug: Thalidomide

Arm VI: TMZ + Thalidomide + Celecoxib

EXPERIMENTAL

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

Drug: Celecoxib; Drug: Temozolomide; Drug: Thalidomide

Arm VII: TMZ + Isotretinoin + Celecoxib

EXPERIMENTAL

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

Drug: Celecoxib; Drug: Isotretinoin; Drug: Temozolomide

Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib

EXPERIMENTAL

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

Drug: Celecoxib; Drug: Isotretinoin; Drug: Temozolomide; Drug: Thalidomide

Interventions

Celecoxib DRUG

400 mg orally twice a day continuous dosing

Also known as: Celebrex

Arm IV: TMZ + Celecoxib; Arm VI: TMZ + Thalidomide + Celecoxib; Arm VII: TMZ + Isotretinoin + Celecoxib; Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib

Isotretinoin DRUG

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

Also known as: Accutane, 13-Cis-Retinoic Acid

Arm III: TMZ + Isotretinoin; Arm V: TMZ + Thalidomide + Isotretinoin; Arm VII: TMZ + Isotretinoin + Celecoxib; Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib

Temozolomide DRUG

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

Also known as: Temodar

Arm I: TMZ; Arm II: TMZ + Thalidomide; Arm III: TMZ + Isotretinoin; Arm IV: TMZ + Celecoxib; Arm V: TMZ + Thalidomide + Isotretinoin; Arm VI: TMZ + Thalidomide + Celecoxib; Arm VII: TMZ + Isotretinoin + Celecoxib; Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib

Thalidomide 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)

Also known as: Thalomid

Arm II: TMZ + Thalidomide; Arm V: TMZ + Thalidomide + Isotretinoin; Arm VI: TMZ + Thalidomide + Celecoxib; Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (12)

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

Fort Smith, Arkansas, 72913, United States

Location

University of Texas MD Anderson Cancer Center at Orlando

Orlando, Florida, 32806-2134, United States

Location

CCOP - Atlanta Regional

Atlanta, Georgia, 30342-1701, United States

Location

CCOP - Central Illinois

Decatur, Illinois, 62526, United States

Location

CCOP - Wichita

Wichita, Kansas, 67214-3882, United States

Location

CCOP - Grand Rapids

Grand Rapids, Michigan, 49503, United States

Location

CCOP - Kalamazoo

Kalamazoo, Michigan, 49007-3731, United States

Location

CCOP - Kansas City

Kansas City, Missouri, 64131, United States

Location

Cancer Research for the Ozarks

Springfield, Missouri, 65804, United States

Location

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

Columbus, Ohio, 43210-1240, United States

Location

CCOP - Upstate Carolina

Spartanburg, South Carolina, 29303, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Related Publications (2)

• 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.

  PMID: 20729242 RESULT

• 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.

  PMID: 25239666 DERIVED

Related Links

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

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma

Interventions

Celecoxib; Isotretinoin; Temozolomide; Thalidomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Pigments, Biological; Biological Factors; Dacarbazine; Triazenes; Imidazoles; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: John F de Groot, Chair Ad Interim, Neuro-Oncology
• Organization: The University of Texas (UT) MD Anderson Cancer Center

jdegroot@mdanderson.org

713-745-3072

Study Officials

• Marta Penas-Prado, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2005
• First Posted: June 3, 2005
• Study Start: September 1, 2005
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 18, 2021
• Results First Posted: October 18, 2021

Record last verified: 2021-09

Locations

US (12)