Temozolomide and Radiation Therapy in Treating Patients With Gliomas

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00114140
• Other study ID #: RTOG 0424
• Secondary ID: CDR0000434849NCI
• Status: Completed
• Phase: Phase 2
• Start date: January 2005
• Est. completion date: May 20, 2022

Study information

• Verified date: May 2022
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: May 20, 2022
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioma
• Nervous System Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Canada	Hopital Notre-Dame du CHUM	Montreal	Quebec
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
United States	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	DeCesaris Cancer Institute at Anne Arundel Medical Center	Annapolis	Maryland
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Baptist Medical Center South	Jacksonville	Florida
United States	Integrated Community Oncology Network at Southside Cancer Center	Jacksonville	Florida
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Integrated Community Oncology Network	Jacksonville Beach	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Integrated Community Oncology Network - Orange Park	Orange Park	Florida
United States	Florida Cancer Center - Palatka	Palatka	Florida
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Arizona Oncology Services Foundation	Phoenix	Arizona
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Flagler Cancer Center	Saint Augustine	Florida
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Cancer Treatment Center	Wooster	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Registration to 3 years
Primary	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.	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.
Primary	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.	Registration to 3 years
Primary	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%.	Baseline, 6 months, and 12 months.
Primary	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.	Baseline, 6 months, and 12 months.