Brain and Central Nervous System TumorsPhase 2NCT00112502
Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme
A Phase 2 study testing Celecoxib, Isotretinoin and Temozolomide in people with Brain and Central Nervous System Tumors and Glioblastoma Multiforme, run by M.D. Anderson Cancer Center at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain and Central Nervous System Tumors, Glioblastoma Multiforme
- What is being tested?
- Celecoxib, Isotretinoin and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 178 participants
- Where
- 12 sitesUnited States
- Study dates
- Sep 2005to Sep 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
CCOP - Atlanta Regional
Atlanta, Georgia, 30342-1701
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210-1240
CCOP - Central Illinois
Decatur, Illinois, 62526
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
Fort Smith, Arkansas, 72913
CCOP - Grand Rapids
Grand Rapids, Michigan, 49503
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4009
CCOP - Kalamazoo
Kalamazoo, Michigan, 49007-3731
CCOP - Kansas City
Kansas City, Missouri, 64131
University of Texas MD Anderson Cancer Center at Orlando
Orlando, Florida, 32806-2134
CCOP - Upstate Carolina
Spartanburg, South Carolina, 29303
Cancer Research for the Ozarks
Springfield, Missouri, 65804
CCOP - Wichita
Wichita, Kansas, 67214-3882
About this study
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
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.
Read the 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.
- Being tested
- Celecoxib, Isotretinoin, Temozolomide, Thalidomide
- Keywords
- adult giant cell glioblastoma, adult gliosarcoma, adult glioblastoma
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CelecoxibDrug
Also called Celebrex
400 mg orally twice a day continuous dosing
IsotretinoinDrug
Also called Accutane, 13-Cis-Retinoic Acid
40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle.
TemozolomideDrug
Also called Temodar
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
ThalidomideDrug
Also called Thalomid
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)
| Study group | Role | What they receive |
|---|---|---|
| Arm I: TMZ | Active comparator | Oral Temozolomide (TMZ) 150 mg/m^2 once daily on days 1-7 and 15-21. Receives: 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). Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Celecoxib; Drug: Isotretinoin; Drug: Temozolomide; Drug: Thalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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
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).
Measured: 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
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).
Measured: 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
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).
Measured: 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
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).
Measured: 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
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).
Measured: Every 3 months from randomization until progression of disease, death or last follow-up.
Median Overall Survival (OS) Comparison of Doublet Versus Triplet Therapy
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).
Measured: Every 3 months from randomization until progression of disease, death or last follow-up.
Overall Survival of Individual Arms
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).
Measured: Every 3 months from randomization until progression of disease, death or last follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2005 (estimated)
- Study startSep 2005
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 178 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Marta Penas-Prado, MD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00112502
- Sponsor's protocol ID
- 2004-0662
- Other IDs
- MDA-ID-02586, NCI-6636, MDA-2004-0662, CDR0000432954, NCI-2009-00076
- Status last verified
- Sep 2021
- First submitted
- 2 Jun 2005
- Last updated
- 18 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 20729242Penas-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.
PubMed 25239666
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00112502
- Acronym / sponsor ID
- 2004-0662
- Keywords
- adult giant cell glioblastoma, adult gliosarcoma, adult glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 178 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2005
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 3 Jun 2005 (estimated)
- Results
- Posted 18 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Arm I: TMZ | Active comparator | Drug: TemozolomideOral Temozolomide (TMZ) 150 mg/m^2 once daily on days 1-7 and 15-21. |
| Arm II: TMZ + Thalidomide | Experimental | Drug: Temozolomide, Drug: ThalidomideTemozolomide as in arm I and oral Thalidomide (Thal) once daily on days 1-28 (starting dose 200 mg). |
| Arm III: TMZ + Isotretinoin | Experimental | Drug: Isotretinoin, Drug: TemozolomideTemozolomide as in Arm I and oral Isotretinoin 40 mg/m^2 twice daily on days 1-21. |
| Arm IV: TMZ + Celecoxib | Experimental | Drug: Celecoxib, Drug: TemozolomideTemozolomide as in arm I and oral Celecoxib 400 mg twice daily on days 1-28. |
| Arm V: TMZ + Thalidomide + Isotretinoin | Experimental | Drug: Isotretinoin, Drug: Temozolomide, Drug: ThalidomideTemozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III. |
| Arm VI: TMZ + Thalidomide + Celecoxib | Experimental | Drug: Celecoxib, Drug: Temozolomide, Drug: ThalidomideTemozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV. |
| Arm VII: TMZ + Isotretinoin + Celecoxib | Experimental | Drug: Celecoxib, Drug: Isotretinoin, Drug: TemozolomideTemozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV. |
| Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib | Experimental | Drug: Celecoxib, Drug: Isotretinoin, Drug: Temozolomide, Drug: ThalidomideTemozolomide as in Arm I, Thalidomide as in Arm II, Isotretinoin as in Arm III, and Celecoxib as in Arm IV. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CelecoxibAlso: Celebrex400 mg orally twice a day continuous dosing | Drug | Arm IV: TMZ + Celecoxib, Arm VI: TMZ + Thalidomide + Celecoxib, Arm VII: TMZ + Isotretinoin + Celecoxib, Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib |
| IsotretinoinAlso: Accutane, 13-Cis-Retinoic Acid40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Drug | Arm III: TMZ + Isotretinoin, Arm V: TMZ + Thalidomide + Isotretinoin, Arm VII: TMZ + Isotretinoin + Celecoxib, Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib |
| TemozolomideAlso: Temodar150 mg/m2 orally daily, 7 days on treatment, 7 days off. | Drug | 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 |
| ThalidomideAlso: Thalomid400 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) | Drug | Arm II: TMZ + Thalidomide, Arm V: TMZ + Thalidomide + Isotretinoin, Arm VI: TMZ + Thalidomide + Celecoxib, Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib |
Primary outcome
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).
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).
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).
7 secondary outcomes
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.
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 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.
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.
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.
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.
Overall Survival of Individual Arms
Time frame: Every 3 months from randomization until progression of disease, death or last follow-up.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20729242Gilbert 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.
- Derived from this study: PubMed 25239666Penas-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.
- University of Texas (UT) MD Anderson Cancer Center Official WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marta Penas-Prado, MD study chair
M.D. Anderson Cancer Center
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Celecoxib, Isotretinoin and Temozolomide in people with Brain and Central Nervous System Tumors and Glioblastoma Multiforme, run by M.D. Anderson Cancer Center at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00112502, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2021.