Temozolomide and Radiation Therapy in Treating Patients With Gliomas

NCT00114140 | Completed Phase 2 Results DMC

• 3 other identifiers: RTOG 0424CDR0000434849NCI-2009-00723
• Study Type: interventional
• Target: 136
• Locations: 2 countries
• Sites: 47

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult diffuse astrocytoma; adult oligodendroglioma; adult mixed glioma

Outcome Measures

Primary Outcomes (5)

• 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

• 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.

• 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

• 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.

• 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.

Study Arms (1)

Temozolomide + Radiation Therapy (RT)

EXPERIMENTAL

Daily temozolomide plus concurrent radiotherapy followed by temozolomide

Drug: Temozolomide; Radiation: Radiation therapy

Interventions

Temozolomide 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.

Temozolomide + Radiation Therapy (RT)

Radiation therapy RADIATION

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

Temozolomide + Radiation Therapy (RT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• NRG Oncology: collaborator

Study Sites (47)

Arizona Oncology Services Foundation

Phoenix, Arizona, 85013, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, 32207, United States

Location

Integrated Community Oncology Network at Southside Cancer Center

Jacksonville, Florida, 32207, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Baptist Medical Center South

Jacksonville, Florida, 32258, United States

Location

Integrated Community Oncology Network

Jacksonville Beach, Florida, 32250, United States

Location

Integrated Community Oncology Network - Orange Park

Orange Park, Florida, 32073, United States

Location

Florida Cancer Center - Palatka

Palatka, Florida, 32177, United States

Location

Flagler Cancer Center

Saint Augustine, Florida, 32086, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

DeCesaris Cancer Institute at Anne Arundel Medical Center

Annapolis, Maryland, 21401, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0942, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Sparrow Regional Cancer Center

Lansing, Michigan, 48912-1811, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

CCOP - Kansas City

Kansas City, Missouri, 64131, United States

Location

Methodist Estabrook Cancer Center

Omaha, Nebraska, 68114, United States

Location

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Mission Hospitals - Memorial Campus

Asheville, North Carolina, 28801, United States

Location

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, 44309-2090, United States

Location

Aultman Cancer Center at Aultman Hospital

Canton, Ohio, 44710-1799, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

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

Columbus, Ohio, 43210-1240, United States

Location

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

Salem, Ohio, 44460, United States

Location

Cancer Treatment Center

Wooster, Ohio, 44691, United States

Location

Rosenfeld Cancer Center at Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, 19107-5541, United States

Location

CCOP - Upstate Carolina

Spartanburg, South Carolina, 29303, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, 84157, United States

Location

Dixie Regional Medical Center - East Campus

St. George, Utah, 84770, United States

Location

University Cancer Center at University of Washington Medical Center

Seattle, Washington, 98195-6043, United States

Location

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

Green Bay, Wisconsin, 54301-3526, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

Gundersen Lutheran Center for Cancer and Blood

La Crosse, Wisconsin, 54601, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, 54143, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Hopital Notre-Dame du CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

McGill Cancer Centre at McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Related Publications (1)

• 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.

  PMID: 29955793 DERIVED

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Oligodendroglioma; Glioma

Interventions

Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Limitations and Caveats

Quality of life endpoint was added via an amendment while study was in progress.

Results Point of Contact

• Title: Wendy Seiferheld, M.S.
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• Barbara J. Fisher, MD

  London Health Sciences Centre

  PRINCIPAL INVESTIGATOR

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2005
• First Posted: June 14, 2005
• Study Start: January 1, 2005
• Primary Completion: February 1, 2013
• Study Completion: May 20, 2022
• Last Updated: July 8, 2024
• Results First Posted: November 6, 2017

Record last verified: 2022-05

Locations

US (45); CA (2)