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Temozolomide and Radiation Therapy in Treating Patients With Gliomas

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00114140
First Posted: June 14, 2005
Last Update Posted: November 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors Drug: Temozolomide Radiation: Radiation therapy Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of a Temozolomide-Based Chemoradiotherapy Regimen for High-Risk Low-Grade Gliomas

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Overall Survival Rate at 3 Years [ Time Frame: Registration to 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.

  • Progression-free Survival [ Time Frame: Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.) ]
    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.

  • Survival and Progression-free Survival by O(6)-Methylguanine-DNA Methyltransferase (MGMT) Methylation Status [ Time Frame: Registration to 3 years ]
    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.

  • Quality of Life as Measured by the Functional Assessment of Cancer Therapy Scale With Brain Module (FACT-BR) [ Time Frame: Baseline, 6 months, and 12 months. ]
    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%.

  • Neurocognitive Function [ Time Frame: Baseline, 6 months, and 12 months. ]
    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.


Enrollment: 136
Study Start Date: January 2005
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Temozolomide + Radiation Therapy (RT)
Daily temozolomide plus concurrent radiotherapy followed by temozolomide
Drug: Temozolomide

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

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00114140


  Show 47 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Investigators
Principal Investigator: Barbara J. Fisher, MD London Health Sciences Centre
Study Chair: David R. Macdonald, MD, FRCPC London Health Sciences Centre
Study Chair: Glenn J. Lesser, MD Wake Forest University Health Sciences
Study Chair: Stephen W. Coons, MD St. Joseph's Hospital and Medical Center, Phoenix
  More Information

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00114140     History of Changes
Other Study ID Numbers: RTOG 0424
CDR0000434849
NCI-2009-00723 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: June 13, 2005
First Posted: June 14, 2005
Results First Submitted: January 17, 2017
Results First Posted: November 6, 2017
Last Update Posted: November 6, 2017
Last Verified: October 2017

Keywords provided by Radiation Therapy Oncology Group:
adult diffuse astrocytoma
adult oligodendroglioma
adult mixed glioma

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents