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Temozolomide and Radiation Therapy in Treating Patients With Gliomas

Phase 2
Completed
Conditions
Brain and Central Nervous System Tumors
Interventions
Drug: Temozolomide
Radiation: Radiation therapy
Registration Number
NCT00114140
Lead Sponsor
Radiation Therapy Oncology Group
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
136
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Temozolomide + Radiation Therapy (RT)Radiation therapyDaily temozolomide plus concurrent radiotherapy followed by temozolomide
Temozolomide + Radiation Therapy (RT)TemozolomideDaily temozolomide plus concurrent radiotherapy followed by temozolomide
Primary Outcome Measures
NameTimeMethod
Neurocognitive FunctionBaseline, 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.

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

Overall Survival Rate at 3 YearsRegistration 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 SurvivalFrom registration to last follow-up, up to 7.1 years. Analysis occurs after all patients have been on study for at least 3 years.

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.

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

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (47)

USC/Norris Comprehensive Cancer Center and Hospital

🇺🇸

Los Angeles, California, United States

Integrated Community Oncology Network

🇺🇸

Jacksonville Beach, Florida, United States

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

🇺🇸

Columbus, Ohio, United States

Greenebaum Cancer Center at University of Maryland Medical Center

🇺🇸

Baltimore, Maryland, United States

University Cancer Center at University of Washington Medical Center

🇺🇸

Seattle, Washington, United States

Rosenfeld Cancer Center at Abington Memorial Hospital

🇺🇸

Abington, Pennsylvania, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Arizona Oncology Services Foundation

🇺🇸

Phoenix, Arizona, United States

Josephine Ford Cancer Center at Henry Ford Hospital

🇺🇸

Detroit, Michigan, 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

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

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

🇺🇸

Salem, Ohio, United States

Summa Center for Cancer Care at Akron City Hospital

🇺🇸

Akron, Ohio, United States

Gundersen Lutheran Center for Cancer and Blood

🇺🇸

La Crosse, Wisconsin, United States

West Michigan Cancer Center

🇺🇸

Kalamazoo, Michigan, United States

Cancer Treatment Center

🇺🇸

Wooster, Ohio, United States

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

🇺🇸

Murray, Utah, United States

Dixie Regional Medical Center - East Campus

🇺🇸

Saint George, Utah, United States

Rapid City Regional Hospital

🇺🇸

Rapid City, South Dakota, United States

Mission Hospitals - Memorial Campus

🇺🇸

Asheville, North Carolina, United States

St. Vincent Hospital Regional Cancer Center

🇺🇸

Green Bay, Wisconsin, United States

Hopital Notre-Dame du CHUM

🇨🇦

Montreal, Quebec, Canada

Methodist Estabrook Cancer Center

🇺🇸

Omaha, Nebraska, United States

Medical College of Wisconsin Cancer Center

🇺🇸

Milwaukee, Wisconsin, United States

University of Michigan Comprehensive Cancer Center

🇺🇸

Ann Arbor, Michigan, United States

Mayo Clinic Cancer Center

🇺🇸

Rochester, Minnesota, United States

CCOP - Kansas City

🇺🇸

Kansas City, Missouri, United States

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

🇺🇸

Green Bay, Wisconsin, United States

Mayo Clinic - Jacksonville

🇺🇸

Jacksonville, Florida, United States

Florida Cancer Center - Palatka

🇺🇸

Palatka, Florida, United States

McGill Cancer Centre at McGill University

🇨🇦

Montreal, Quebec, Canada

CCOP - Christiana Care Health Services

🇺🇸

Newark, Delaware, United States

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Baptist Cancer Institute - Jacksonville

🇺🇸

Jacksonville, Florida, United States

Integrated Community Oncology Network at Southside Cancer Center

🇺🇸

Jacksonville, Florida, United States

Integrated Community Oncology Network - Orange Park

🇺🇸

Orange Park, Florida, United States

Flagler Cancer Center

🇺🇸

Saint Augustine, Florida, United States

Baptist Medical Center South

🇺🇸

Jacksonville, Florida, United States

Sparrow Regional Cancer Center

🇺🇸

Lansing, Michigan, United States

CCOP - Upstate Carolina

🇺🇸

Spartanburg, South Carolina, United States

DeCesaris Cancer Institute at Anne Arundel Medical Center

🇺🇸

Annapolis, Maryland, United States

Bay Area Cancer Care Center at Bay Area Medical Center

🇺🇸

Marinette, Wisconsin, United States

University of Florida Shands Cancer Center

🇺🇸

Gainesville, Florida, United States

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

🇺🇸

Madison, Wisconsin, United States

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