Temozolomide and Radiation Therapy in Treating Patients With Gliomas

NCT ID: NCT00114140

Last Updated: 2024-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2022-05-20

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Temozolomide + Radiation Therapy (RT)

Daily temozolomide plus concurrent radiotherapy followed by temozolomide

Group Type: EXPERIMENTAL

Temozolomide

Intervention Type: DRUG

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 therapy

Intervention Type: RADIATION

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

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NRG Oncology

OTHER

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Barbara J. Fisher, MD

Role: PRINCIPAL_INVESTIGATOR

London Health Sciences Centre

David R. Macdonald, MD, FRCPC

Role: STUDY_CHAIR

London Health Sciences Centre

Glenn J. Lesser, MD

Role: STUDY_CHAIR

Wake Forest University Health Sciences

Stephen W. Coons, MD

Role: STUDY_CHAIR

St. Joseph's Hospital and Medical Center, Phoenix

Locations

Arizona Oncology Services Foundation

Phoenix, Arizona, United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, United States

Integrated Community Oncology Network at Southside Cancer Center

Jacksonville, Florida, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Baptist Medical Center South

Jacksonville, Florida, United States

Integrated Community Oncology Network

Jacksonville Beach, Florida, United States

Integrated Community Oncology Network - Orange Park

Orange Park, Florida, United States

Florida Cancer Center - Palatka

Palatka, Florida, United States

Flagler Cancer Center

Saint Augustine, Florida, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

DeCesaris Cancer Institute at Anne Arundel Medical Center

Annapolis, Maryland, United States

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Sparrow Regional Cancer Center

Lansing, Michigan, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

CCOP - Kansas City

Kansas City, Missouri, United States

Methodist Estabrook Cancer Center

Omaha, Nebraska, United States

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Mission Hospitals - Memorial Campus

Asheville, North Carolina, United States

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States

Aultman Cancer Center at Aultman Hospital

Canton, Ohio, 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

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

Salem, Ohio, United States

Cancer Treatment Center

Wooster, Ohio, 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

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, United States

Dixie Regional Medical Center - East Campus

St. George, Utah, United States

University Cancer Center at University of Washington Medical Center

Seattle, Washington, 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

Gundersen Lutheran Center for Cancer and Blood

La Crosse, Wisconsin, 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

Hopital Notre-Dame du CHUM

Montreal, Quebec, Canada

McGill Cancer Centre at McGill University

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 29955793 (View on PubMed)

Other Identifiers

CDR0000434849

Identifier Type: -

Identifier Source: secondary_id

NCI-2009-00723

Identifier Type: REGISTRY

Identifier Source: secondary_id

RTOG 0424

Identifier Type: -

Identifier Source: org_study_id