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Brain and Central Nervous System TumorsPhase 2NCT00114140

Temozolomide and Radiation Therapy in Treating Patients With Gliomas

A Phase 2 study testing Temozolomide and Radiation therapy in people with Brain and Central Nervous System Tumors, run by Radiation Therapy Oncology Group at 47 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Radiation therapy uses high-energy x-rays to kill tumor cells. 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
What is being tested?
Temozolomide and Radiation therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
136 participants
Where
47 sitesin 2 countries
Study dates
Jan 2005to 20 May 2022
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 glioma of 1 of the following histologies:
  • Astrocytoma (diffuse fibrillary, protoplasmic, or gemistocytic)
  • Oligodendroglioma
  • Oligoastrocytoma Note: *Histologic atypia allowed provided no other histologic features (i.e., frequent mitoses, endothelial proliferation, and/or acute necrosis) that would result in a designation of anaplastic astrocytoma, anaplastic mixed oligodendroglioma or oligoastrocytoma, or glioblastoma multiforme are present
  • Unifocal or multifocal disease
  • World Health Organization (WHO) grade II disease
  • Neurofibromatosis allowed
  • Surgical biopsy or resection for tumor tissue sampling required within the past 12 weeks
  • Tissue block or core biopsy available for O6-methylguanine-DNA methyltransferase analysis and tissue banking
  • Patients who have only had a stereotactic biopsy are not eligible
  • Must have ≥ 3 of the following risk factors:
  • Age 40 and over
  • Largest preoperative tumor diameter ≥ 6 cm
  • Tumor crosses the midline
  • Astrocytoma-dominant tumor subtype
  • Preoperative Neurological Function Status > 1
  • No other low-grade glioma histologies, including any of the following:
  • Pilocytic astrocytoma
  • Subependymal giant cell astrocytoma of tuberous sclerosis
  • Subependymoma
  • Pleomorphic xanthoastrocytoma
  • Presence of a neuronal element, such as ganglioglioma
  • Dysneuroembryoplastic epithelial tumor
  • No high-grade glioma, including any of the following:
  • Anaplastic astrocytoma
  • Glioblastoma multiforme
  • Anaplastic oligodendroglioma
  • Anaplastic oligoastrocytoma
  • No tumors in any non-supratentorial location, including any of the following:
  • Optic chiasm
  • Optic nerve(s)
  • Pons
  • Medulla
  • Cerebellum
  • Spinal cord
  • No evidence of disease progression to spinal meninges or noncontiguous cranial meninges (i.e., leptomeningeal gliomatosis) by MRI of the spine or cerebrospinal fluid (CSF) cytology
  • MRI of the spine or CSF cytology are not required for patients without symptoms of spinal/cranial meningeal disease progression

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Total bilirubin ≤ 1.5 mg/dL
  • Serum glutamate oxaloacetate transaminase (SGOT) or Serum glutamate pyruvate transaminase (SGPT) ≤ 2 times normal
  • Alkaline phosphatase ≤ 2 times normal

Renal

  • Serum creatinine ≤ 1.5 mg/dL

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known HIV positivity
  • No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer
  • No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunotherapy or biologic therapy

Chemotherapy

  • No prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy to the head and neck unless head and neck radiotherapy clearly excluded the brain (e.g., localized radiotherapy to the vocal cords)
  • No prior radiotherapy to the brain
  • No concurrent intensity modulated radiotherapy
  • No concurrent stereotactic boost radiotherapy

Surgery

  • See Disease Characteristics

Other

  • No other concurrent investigational agents

Trial locations and contacts

47 sites in 2 countries.

47 sites in 2 countries

United States45 sites

  • Rosenfeld Cancer Center at Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • Summa Center for Cancer Care at Akron City Hospital

    Akron, Ohio, 44309-2090

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109-0942

  • DeCesaris Cancer Institute at Anne Arundel Medical Center

    Annapolis, Maryland, 21401

  • Mission Hospitals - Memorial Campus

    Asheville, North Carolina, 28801

  • Greenebaum Cancer Center at University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Aultman Cancer Center at Aultman Hospital

    Canton, Ohio, 44710-1799

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60637-1470

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

    Columbus, Ohio, 43210-1240

  • Josephine Ford Cancer Center at Henry Ford Hospital

    Detroit, Michigan, 48202

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center

    Green Bay, Wisconsin, 54301-3526

  • St. Vincent Hospital Regional Cancer Center

    Green Bay, Wisconsin, 54307-3508

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Baptist Cancer Institute - Jacksonville

    Jacksonville, Florida, 32207

  • Integrated Community Oncology Network at Southside Cancer Center

    Jacksonville, Florida, 32207

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

  • Baptist Medical Center South

    Jacksonville, Florida, 32258

  • Integrated Community Oncology Network

    Jacksonville Beach, Florida, 32250

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007-3731

  • CCOP - Kansas City

    Kansas City, Missouri, 64131

  • Gundersen Lutheran Center for Cancer and Blood

    La Crosse, Wisconsin, 54601

  • Sparrow Regional Cancer Center

    Lansing, Michigan, 48912-1811

  • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756-0002

  • USC/Norris Comprehensive Cancer Center and Hospital

    Los Angeles, California, 90089-9181

  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

    Madison, Wisconsin, 53792-6164

  • Bay Area Cancer Care Center at Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • Medical College of Wisconsin Cancer Center

    Milwaukee, Wisconsin, 53226

  • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

    Murray, Utah, 84157

  • CCOP - Christiana Care Health Services

    Newark, Delaware, 19713

  • Methodist Estabrook Cancer Center

    Omaha, Nebraska, 68114

  • Integrated Community Oncology Network - Orange Park

    Orange Park, Florida, 32073

  • Florida Cancer Center - Palatka

    Palatka, Florida, 32177

  • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

    Philadelphia, Pennsylvania, 19107-5541

  • Arizona Oncology Services Foundation

    Phoenix, Arizona, 85013

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Flagler Cancer Center

    Saint Augustine, Florida, 32086

  • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford

    Salem, Ohio, 44460

  • University Cancer Center at University of Washington Medical Center

    Seattle, Washington, 98195-6043

  • CCOP - Upstate Carolina

    Spartanburg, South Carolina, 29303

  • Dixie Regional Medical Center - East Campus

    St. George, Utah, 84770

  • Cancer Treatment Center

    Wooster, Ohio, 44691

Other trials in United States

Canada2 sites

  • Hopital Notre-Dame du CHUM

    Montreal, Quebec, H2L 4M1

  • McGill Cancer Centre at McGill University

    Montreal, Quebec, H2W 1S6

Other trials in Canada

About this study

Official title: A Phase II Study of a Temozolomide-Based Chemoradiotherapy Regimen for High-Risk Low-Grade Gliomas

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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving temozolomide together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving temozolomide together with radiation therapy works in treating patients with low-grade gliomas.

Read the detailed description

OBJECTIVES:

  • Compare the 3-year survival of patients with high-risk low-grade gliomas treated with temozolomide and radiotherapy followed by temozolomide alone with that of patients enrolled on European Organization for Research and Treatment of Cancer (EORTC)clinical trials EORTC-22844 and EORTC-22845.
  • Determine the toxicity of this regimen in these patients.
  • Determine the association between progression-free survival and O6-methylguanine-DNA methyltransferase (MGMT) methylation status in patients treated with this regimen.
  • Determine the association between survival and MGMT methylation status in patients treated with this regimen.
  • Determine the quality of life (QOL) of patients treated with this regimen.
  • Determine the neurocognitive function of patients treated with this regimen.
  • Evaluate the feasibility of collecting patient-reported QOL and neurocognitive assessments over 3 years.

OUTLINE: This is a non-randomized, multicenter study.

Patients receive oral temozolomide once daily on days 1-42 and undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40, one hour before RT weekdays, in the evening weekends. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 6 months, 12 months.

After completion of study treatment, patients are followed at 4 months, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 135 patients will be accrued for this study within 44 months.

Being tested
Temozolomide, Radiation therapy
Keywords
adult diffuse astrocytoma, adult oligodendroglioma, adult mixed glioma
Medical subject headings
Central Nervous System Neoplasms, Astrocytoma, Oligodendroglioma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TemozolomideDrug

    Concurrent chemoradiotherapy temozolomide given 75 mg/m^2 daily during radiotherapy for 6 weeks.

    Post-Radiation Temozolomide given 150 mg/m2 daily on days 1-5 every 28 days with cycle one beginning 28 days post-radiotherapy. In the absence of grade 3 or 4 adverse events, a single dose escalation to 200 mg/m2/day could be attempted for cycle 2 and, if tolerated, that dose should continue for all subsequent cycles. Cycles were repeated every 28 days (+/- 2 days) for a total of 12 cycles.

  • Radiation therapyRadiation

    One treatment of 1.8 Gy given daily, 5 days per week (over 6 weeks) for a total dose of 54.0 Gy.

Study groups in NCT00114140
Study groupRoleWhat they receive
Temozolomide + Radiation Therapy (RT)ExperimentalDaily temozolomide plus concurrent radiotherapy followed by temozolomide
Receives: Drug: Temozolomide; Radiation: Radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival Rate at 3 Years

    Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 3 years.

    Measured: Registration to 3 years

  2. Progression-free Survival

    Progressive Disease (PD) is defined as 25% or > increase in the cross-sectional area of enhancing or non-enhancing tumor on consecutive MRI scans, or any new area(s) of tumor. Under exceptional circumstances, disease progression may be declared in the absence of an increase in tumor size based on "clinical deterioration" including the need for increasing doses of steroid and/or a worsening Karnofsky Performance Status(KPS) / Neurologic Function Score(NFS). Progression-free survival time is defined as time from registration to date of progressive disease or death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Median survival time is reported.

    Measured: From registration to last follow-up, up to 7.1 years. Analysis occurs after all patients have been on study for at least 3 years.

  3. Survival and Progression-free Survival by O(6)-Methylguanine-DNA Methyltransferase (MGMT) Methylation Status

    Survival time is defined as time from registration to date of death from any cause. Progressive Disease (PD) is defined as 25% or > increase in the cross-sectional area of enhancing or non-enhancing tumor on consecutive MRI scans, or any new area(s) of tumor. Under exceptional circumstances, disease progression may be declared in the absence of an increase in tumor size based on "clinical deterioration" including the need for increasing doses of steroid and/or a worsening Karnofsky Performance Status(KPS) / Neurologic Function Score(NFS). Survival and progression-free survival are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.

    Measured: Registration to 3 years

  4. Quality of Life as Measured by the Functional Assessment of Cancer Therapy Scale With Brain Module (FACT-BR)

    Functional Assessment of Cancer Therapy Scale with brain module (FACT-BR): a 50-question self-report questionnaire contains the following domains (scales): Physical well-being (7 questions totalling 0-28), social/family well-being (7 questions totalling 0-28), emotional well-being (6 questions totalling 0-24), functional well-being (7 questions totalling 0-28) and brain cancer subscale which contains concerns relevant to patients with brain tumors (19 questions totalling 0-76). Each question has a value 0-4. For some questions a higher indicates better outcome and others are the opposite. The former are summed as is, the latter are reversed in value before adding, such that each domain ranges from 0 to 4 multiplied by the number of questions in the domain, with 0 indicating worst and the highest possible value indicating best outcome. The FACT-Br total (0-184) is obtained by adding all domains together if the overall question response rate is greater than 80%.

    Measured: Baseline, 6 months, and 12 months.

  5. Neurocognitive Function

    Hopkins Verbal Learning Test (HVLT) is a test measuring learning memory retrieval, and memory consolidation processes.; Controlled Oral Word Association Test (COWAT) is a test of phonemic verbal fluency. The patient produces as many words as possible in 1 min. (each) for a specific letter (C, F, L or P, R, W).; Trail Making Test (TMT) is a measure of visuospatial scanning, attention, sequencing, and speed in Part A (TMT A) and executive function in Part B (TMT B). Patients must "connect the dots" either in a numbered sequence or alternating letters and numbers. Difference between pre-treatment baseline and follow-up assessment scores determined by the reliable change (RC) index, using a 90% confidence interval to designate statistically significant change.

    Measured: Baseline, 6 months, and 12 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2005 (estimated)
  2. Study startJan 2005
  3. Primary completionFeb 2013
  4. Study completion20 May 2022

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
136 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00114140
Sponsor's protocol ID
RTOG 0424
Other IDs
CDR0000434849, NCI-2009-00723
Status last verified
May 2022
First submitted
13 Jun 2005
Last updated
8 Jul 2024
Data monitoring committee
Yes

Publications

  • Bell EH, Zhang P, Fisher BJ, Macdonald DR, McElroy JP, Lesser GJ, Fleming J, Chakraborty AR, Liu Z, Becker AP, Fabian D, Aldape KD, Ashby LS, Werner-Wasik M, Walker EM, Bahary JP, Kwok Y, Yu HM, Laack NN, Schultz CJ, Gray HJ, Robins HI, Mehta MP, Chakravarti A. Association of MGMT Promoter Methylation Status With Survival Outcomes in Patients With High-Risk Glioma Treated With Radiotherapy and Temozolomide: An Analysis From the NRG Oncology/RTOG 0424 Trial. JAMA Oncol. 2018 Oct 1;4(10):1405-1409. doi: 10.1001/jamaoncol.2018.1977.

    PubMed 29955793

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Temozolomide and Radiation therapy in people with Brain and Central Nervous System Tumors, run by Radiation Therapy Oncology Group at 47 sites in 2 countries.

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 8 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in United States, Canada. 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 6 Nov 2017). 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?

Overall Survival Rate at 3 Years (time frame: Registration to 3 years). The study lists 5 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 NCT00114140, which also lists 1 linked publication.

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 8 Jul 2024.

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