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NCT Number: 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

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.

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Key information

Conditions

Brain and Central Nervous System Tumors Astrocytoma Central Nervous System Neoplasms Glioblastoma Glioblastoma Multiforme Glioma Gliosarcoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Nervous System Diseases Nervous System Neoplasms Neuroectodermal Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center, Fort Smith, Arkansas, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Celecoxib

Drug

400 mg orally twice a day continuous dosing

Other names: Celebrex

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.

Other names: Accutane, 13-Cis-Retinoic Acid

Temozolomide

Drug

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

Other names: Temodar

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)

Other names: Thalomid

Primary outcomes

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

    Time frame: 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).

    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).

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

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

    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).

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

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

    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).

Secondary outcomes

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

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

    Doublet (2 agents) versus Triplet (3 agents) therapy analysis: We compared the median PFS outcome of participants in arms II, III, IV, versus participants in arms V, VI 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).

  2. Median Progression-Free Survival (PFS) of Individual Arms

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

    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).

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

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

    Thalidomide versus not Thalidomide analysis: We compared the median OS outcome of participants in arms II, VI, VII and VIII, versus participants in arms I, III, IV and V. Median OS 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).

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

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

    Celecoxib versus not Celecoxib analysis: We compared the median OS outcome of participants in arms III, V, VI and VIII, versus participants in arms I, II, IV and VII. Median OS 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).

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

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

    Isotretinoin versus not Isotretinoin analysis: We compared the median OS outcome of participants in arms IV, V, VII and VIII, versus participants in arms I, II, III and VI. Median OS 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).

  6. Median Overall Survival (OS) Comparison of Doublet Versus Triplet Therapy

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

    Doublet (2 agents) versus Triplet (3 agents) therapy analysis: We compared the median OS outcome of participants in arms II, III, IV, versus participants in arms V, VI and VII. Median OS 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).

  7. Overall Survival of Individual Arms

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

    Overall Survival (OS) 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).

Sponsors and collaborators

Lead sponsor

M.D. Anderson Cancer Center

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study 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

Important dates

Study start
2005
Primary completion
2014
Study completion
2014
First posted
Jun 3, 2005
Registry last updated
Oct 18, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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