Radiation Therapy (RT) and Temozolomide (TMZ) in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Phase III Trial Comparing Conventional Adjuvant Temozolomide With Dose-Intensive Temozolomide in Patients With Newly Diagnosed Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00304031
• Other study ID #: RTOG-0525
• Secondary ID: CDR0000465183EOR
• Status: Completed
• Phase: Phase 3
• Start date: January 2006
• Est. completion date: December 2016

Study information

• Verified date: May 2020
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving radiation therapy together with temozolomide may kill more tumor cells. It is not yet known which schedule of temozolomide when given together with radiation therapy is more effective in treating glioblastoma or gliosarcoma.

PURPOSE: This randomized phase III trial is studying two different schedules of temozolomide to compare how well they work when given together with radiation therapy in treating patients with newly diagnosed glioblastoma or gliosarcoma.

Description:

OBJECTIVES:

Primary

• Determine if dose-intensifying (increasing the "dose-density") the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy as measured by overall survival of patients with newly diagnosed glioblastoma or gliosarcoma.

Secondary

• Determine if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy as measured by progression-free survival.

• Determine in patients with unmethylated MGMT (O-6-methylguanine-DNA methyltransferase) if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy (overall and progression-free survival) compared with patients receiving conventional temozolomide dosing.

• Determine in patients with methylated MGMT if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy (overall and progression-free survival) compared with patients receiving conventional temozolomide dosing.

• Determine if there is an association between tumor MGMT gene methylation status and treatment response.

• Compare and record the toxicities of the conventional and dose-intense chemotherapy regimens.

• Evaluate whether 6-month progression-free survival is associated with overall survival.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to recursive partitioning analysis class (III vs IV vs V), MGMT gene methylation status (methylated vs nonmethylated vs indeterminate), and radiotherapy criteria used (standard vs revised European).

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 2 years, and then every 6 months thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1173
• Est. completion date: December 2016
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

Inclusion criteria:

1. Histopathologically proven diagnosis of glioblastoma. Since gliosarcoma is a variant of glioblastoma, gliosarcoma is also an eligible diagnosis.

2. Patients must have at least 1 block of tissue available for analysis of MGMT status; fresh frozen tumor tissue acquisition is encouraged.

3. Diagnosis must be established by open biopsy or tumor resection. Patients who have only had a stereotactic biopsy are not eligible.

4. The tumor must have a supratentorial component.

5. Patients must have recovered from the effects of surgery, postoperative infection, and other complications before study registration.

6. A diagnostic contrast-enhanced magnetic resonance imaging (MRI) or computerized tomography (CT) scan (if MRI is not available) of the brain must be performed preoperatively and postoperatively. The postoperative scan must be done within 28 days of registration and prior to the initiation of radiotherapy. Preoperative and postoperative scans must be the same type. If CT scans were performed perioperatively, a CT and an MRI should be performed before randomization.

6.1. Patients unable to undergo MRI imaging because of non-compatible devices can be enrolled, provided pre- and post-operative contrast-enhanced CT scans are obtained and are of sufficient quality.

7. Therapy must begin = 5 weeks after the most recent brain tumor surgery.

8. History/physical examination within 14 days prior to study registration.

9. Neurologic examination within 14 days prior to study registration.

10. Documentation of steroid doses within 14 days prior to study registration and stable or decreasing steroid dose within 5 days prior to registration.

11. Karnofsky performance status of = 60.

12. Age = 18 years.

13. Complete blood count (CBC)/differential obtained within 14 days prior to study registration, with adequate bone marrow function as defined below: 13.1 Absolute neutrophil count (ANC) = 1500 cells/mm3. 13.2 Platelets = 100,000 cells/mm3. 13.3 Hemoglobin = 10 g/dl. (Note: The use of transfusion or other intervention to achieve Hgb = 10 g/dl is acceptable.)

14. Adequate renal function, as defined below:

14.1 Blood urea nitrogen (BUN) = 25 mg/dl within 14 days prior to study registration 14.2 Creatinine = 1.7 mg/dl within 14 days prior to study registration

15. Adequate hepatic function, as defined below:

15.1 Bilirubin = 2.0 mg/dl within 14 days prior to study registration 15.2 Alanine aminotransferase (ALT) = 3 x normal range within 14 days prior to study registration 15.3 Aspartate aminotransferase (AST) = 3 x normal range within 14 days prior to study registration

16. Patients must sign a study-specific informed consent prior to study registration.

If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the responsible family member.

17. For females of child-bearing potential, negative serum pregnancy test within 72 hours prior to starting temozolomide.

18. Women of childbearing potential and male participants must practice adequate

Exclusion criteria:

1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for = 3 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible).

2. Recurrent or multifocal malignant gliomas

3. Metastases detected below the tentorium or beyond the cranial vault.

4. Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted. See Section 1.

5. Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.

6. Severe, active co-morbidity, defined as follows:

• 6.1. Unstable angina and/or congestive heart failure requiring hospitalization.

• 6.2. Transmural myocardial infarction within the last 6 months.

• 6.3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.

• 6.4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.

• 6.5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.

• 6.6. Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.

• 6.7. Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.

• 6.8. Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.

7. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

8. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug;

9. Prior allergic reaction to temozolomide.

10. Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.

11. No tissue provided for histopathologic central review and MGMT status.

12. Tissue provided by stereotactic biopsy method.

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Gliosarcoma
• Nervous System Neoplasms

Intervention

Drug:
• Concurrent temozolomide
Daily oral temozolomide (75 mg/m2) up to 49 doses.

Radiation:
• Concurrent radiation therapy
60 Gy in 2 Gy fractions

Drug:
• 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle
Oral temozolomide on days 1-5 of a 28-day cycle. Dose starts at 150mg/m2 for first cycle, increases to 200mg/m2 for subsequent cycles if no unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive up to 6 more courses of temozolomide.
• 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle
Oral temozolomide on days 1-21 of a 28-day cycle. Dose starts at 75mg/m2 for first cycle, increases to 100mg/m2 for subsequent cycles if no unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive up to 6 more courses of temozolomide.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Cancer Care Program at Thunder Bay Regional Health Sciences	Thunder Bay	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	American Fork Hospital	American Fork	Utah
United States	McFarland Clinic, PC	Ames	Iowa
United States	AnMed Cancer Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	DeCesaris Cancer Institute at Anne Arundel Medical Center	Annapolis	Maryland
United States	Theda Care Cancer Institute	Appleton	Wisconsin
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	Piedmont Hospital	Atlanta	Georgia
United States	Auburn Radiation Oncology	Auburn	California
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus	Boca Raton	Florida
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	New York Methodist Hospital	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Radiation Oncology Centers - Cameron Park	Cameron Park	California
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Graham Hospital	Canton	Illinois
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Memorial Hospital	Carthage	Illinois
United States	Sandra L. Maxwell Cancer Center	Cedar City	Utah
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Dartmouth - Hitchcock Concord	Concord	New Hampshire
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Texas Oncology, PA at Texas Cancer Center Dallas Southwest	Dallas	Texas
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Grady Memorial Hospital	Delaware	Ohio
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mercy Capitol Hospital	Des Moines	Iowa
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Dale and Frances Hughes Cancer Center at Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Willamette Valley Cancer Center - Eugene	Eugene	Oregon
United States	Eureka Community Hospital	Eureka	Illinois
United States	Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	St. Francis Hospital	Federal Way	Washington
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Poudre Valley Radiation Oncology	Fort Collins	Colorado
United States	Parkview Regional Cancer Center at Parkview Health	Fort Wayne	Indiana
United States	Radiation Oncology Associates Southwest	Fort Wayne	Indiana
United States	Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital	Fort Worth	Texas
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	InterCommunity Cancer Center of Western Illinois	Galesburg	Illinois
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Cleveland Clinic Cancer Center	Independence	Ohio
United States	Independence Regional Health Center	Independence	Missouri
United States	Central Indiana Cancer Centers - East	Indianapolis	Indiana
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Foote Memorial Hospital	Jackson	Michigan
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	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	St. John's Regional Medical Center	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas City Cancer Centers - South	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Parvin Radiation Oncology	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri
United States	St. Joseph Medical Center	Kansas City	Missouri
United States	Truman Medical Center - Hospital Hill	Kansas City	Missouri
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Kingsbury Center for Cancer Care at Cheshire Medical Center	Keene	New Hampshire
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Cascade Cancer Center at Evergreen Hospital Medical Center	Kirkland	Washington
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Thompson Cancer Survival Center West	Knoxville	Tennessee
United States	Howard Community Hospital	Kokomo	Indiana
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Monter Cancer Center of the North Shore-LIJ Health System	Lake Success	New York
United States	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Southwest Medical Center	Liberal	Kansas
United States	Liberty Hospital	Liberty	Missouri
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	St. Barnabas Medical Center Cancer Center	Livingston	New Jersey
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Kaiser Permanente Medical Center - Los Angeles	Los Angeles	California
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	McDonough District Hospital	Macomb	Illinois
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Riddle Memorial Hospital Cancer Center	Media	Pennsylvania
United States	Community Memorial Hospital Cancer Care Center	Menomonee Falls	Wisconsin
United States	Baptist-South Miami Regional Cancer Program	Miami	Florida
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Upper Delaware Valley Cancer Center	Milford	Pennsylvania
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Intercommunity Cancer Center	Monroeville	Pennsylvania
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	Alle-Kiski Medical Center	Natrona Heights	Pennsylvania
United States	Yale Cancer Center	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Sentara Cancer Institute at Sentara Norfolk General Hospital	Norfolk	Virginia
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Thompson Cancer Survival Center at Methodist	Oak Ridge	Tennessee
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Integrated Community Oncology Network - Orange Park	Orange Park	Florida
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Kansas City Cancer Centers - Southwest	Overland Park	Kansas
United States	Menorah Medical Center	Overland Park	Kansas
United States	Florida Cancer Center - Palatka	Palatka	Florida
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Frankford Hospital Cancer Center - Torresdale Campus	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Arizona Oncology Services Foundation	Phoenix	Arizona
United States	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Adventist Medical Center	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon
United States	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Hudson Valley Oncology Associates	Poughkeepsie	New York
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Lipson Cancer and Blood Center at Rochester General Hospital	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Mercy General Hospital	Sacramento	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Flagler Cancer Center	Saint Augustine	Florida
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Norris Cotton Cancer Center - North	Saint Johnsbury	Vermont
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio
United States	Salem Hospital Regional Cancer Care Services	Salem	Oregon
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Texas Oncology, PA at Texas Cancer Center - Sherman	Sherman	Texas
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Somerset Oncology Center	Somerset	Pennsylvania
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	Frederick R. and Betty M. Smith Cancer Treatment Center	Sparta	New Jersey
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Valley Cancer Center	Spring Valley	Illinois
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Ohio
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Door County Cancer Center at Door County Memorial Hospital	Sturgeon Bay	Wisconsin
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land	Sugar Land	Texas
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Arizona Oncology - Tucson	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Solano Radiation Oncology Center	Vacaville	California
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Wilmed Radiation Oncology Services	Wilson	North Carolina
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Cancer Treatment Center	Wooster	Ohio
United States	CCOP - Main Line Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (4)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	European Organisation for Research and Treatment of Cancer - EORTC, National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

Aldape KD, Jones G, Wang M, et al.: MGMT methylation testing in RTOG 0525: A phase III trial of newly diagnosed glioblastoma. [Abstract] J Clin Oncol 27 (Suppl 15): A-2051, 2009.

Aldape KD, Wang M, Sulman EP, et al.: RTOG 0525: molecular correlates from a randomized phase III trial of newly diagnosed glioblastoma. [Abstract] J Clin Oncol 29 (Suppl 15): A-LBA2000, 2011.

Armstrong TS, Wefel JS, Wang M, et al.: Clinical utility of neurocognitive function (NCF), quality of life (QOL), and symptom assessment as prognostic factors for survival and measures of treatment effects on RTOG 0525. [Abstract] J Clin Oncol 29 (Suppl 1

Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA, Armstrong TS, Wefel JS, Won M, Blumenthal DT, Mahajan A, Schultz CJ, Erridge S, Baumert B, Hopkins KI, Tzuk-Shina T, Brown PD, Chakravarti A, Curran WJ Jr, Mehta MP. Dose-dense temozolomide for — View Citation

Wang M, Dignam J, Won M, et al.: Variation over time and interdependence between disease progression and death among patients with glioblastoma (GBM) on RTOG 0525. [Abstract] J Clin Oncol 29 (Suppl 15): A-2017, 2011.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Overall Survival Time	Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Analysis occurred after 647 deaths were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Secondary	Median Progression-free Survival (PFS) Time	Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of radiation therapy. Analysis occurred after 647 deaths were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Secondary	Median Overall Survival Time by MGMT Status	Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Secondary	Median Progression-free Survival Time by MGMT Status	Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of radiation therapy. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Secondary	Best Treatment Response by MGMT Status	Response assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.0): Complete Response (CR), imaging no longer shows enhancing tumor, confirmed by a second scan = 4 weeks later; Partial Response (PR), >=50% decrease in tumor area (two diameters) with patient off all steroids, or on adrenal maintenance only; Minor Response (MR), < 50% decrease in tumor area with patient off all steroids, or on adrenal maintenance only; Stable Disease (SD): scan shows no change with patient receiving stable/decreasing doses of steroids; Progression (P): > 25% increase in tumor area with no decrease in steroid dose since last evaluation. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Secondary	Distribution of Highest Grade AE Reported as Possibly/Probably/Definitely Related to Protocol Treatment	Highest grade adverse event (AE) per subject was counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Analysis occurred after 647 deaths were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Secondary	Overall Survival Status by Progression Status at 6 Months	Overall survival time is defined as time from registration to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period.	From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Secondary	Mean MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed.	Baseline and cycle 10 (approximately 46 weeks)
Secondary	Mean Neurocognitive Function (NCF) Composite Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy	The NCF Composite score is the arithmetic mean of the Hopkins Verbal Learning Test - Revised (HVLT-R) (Free Recall, Delayed Recall, Delayed Recognition), Trail Making Test Part A (TMTA), Trail Making Test Part B (TMTB), and Controlled Oral Word Association (COWA) test scores, all of which are standardized, adjusting for age, education, and gender as necessary, such that mean is 0 and standard deviation is 1. A participant must have at least 5 of the 6 scores. A higher composite score indicates better neurocognitive function.	Baseline and cycle 10 (approximately 46 weeks)
Secondary	Mean EORTC QLQ-C30 Global Health Status Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy	Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best).	Baseline and cycle 10 (approximately 46 weeks)
Secondary	Mean Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Mid-cyle for Cycle 1	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.	Baseline and mid-cycle 1 (approximately 12 weeks)
Secondary	Mean Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Mid-cyle for Cycle 4	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.	Baseline and mid-cycle 4 (approximately 24 weeks)
Secondary	Mean Change From Baseline in EORTC QLQ-C30 Global Health Status Score at Mid-cyle for Cycle 1	Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.	Baseline and mid-cycle 1 (approximately 12 weeks)
Secondary	Mean Change From Baseline in EORTC QLQ-C30 Global Health Status Score at Mid-cyle for Cycle 4	Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.	Baseline and mid-cycle 4 (approximately 24 weeks)
Secondary	Change From Baseline in Mean EORTC QLQ-C30 Global Health Status	Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change from baseline was calculated as time point value - baseline value with a positive change value indicating improved QOL from baseline.	Baseline, 10,12, 22, 24, and 46 weeks
Secondary	Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Cycle 4	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.	baseline and cycle 4 (approximately 22 weeks)
Secondary	Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Interference Score at Cycle 4	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (did not interfere) to 10 (interfered completely). The symptom interference score is the average of the symptom interference items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.	baseline and cycle 4 (approximately 22 weeks)
Secondary	Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 1	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.; Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration.; The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows.	baseline and cycle 1 (approximately 10 weeks)
Secondary	Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 4	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.; Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration.; The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows.	baseline and cycle 4 (approximately 22 weeks)
Secondary	Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 10	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.; Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration.; The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows.	baseline and cycle 10 (approximately 46 weeks)
Secondary	Mean MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score Over Time	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed.	Baseline, 10, 12, 22, 24, and 46 weeks
Secondary	Determination of Impactful Baseline Instruments on Overall Survival	Overall survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30 subscales are calculated as the mean of component items, then standardized such that subscale scores range from 0 to 100. A high score for a functional scale represents a healthy level of functioning. Controlled Oral Word Association (COWA) score is the sum of correct responses with a range of 0 to infinity. A higher score indicates better functioning. Hopkins Verbal Learning Test - Revised (HVLT-R) score ranges from 0 to 36 for total recall is 0 to 36, 0 to 12 for delayed recall, and -12 to 12 for recognition. A higher score indicates better functioning.	From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Secondary	Mean Neurocognitive Function (NCF) Composite Score Over Time	The NCF Composite score is the arithmetic mean of the HVLT-R (Free Recall, Delayed Recall, Delayed Recognition), TMTA, TMTB, and COWA scores, all of which are standardized, adjusting for age, education, and gender as necessary, such that mean is 0 and standard deviation is 1. A participant must have at least 5 of the 6 scores. A higher composite score indicates better neurocognitive function.	Baseline, 10, 22, and 46 weeks
Secondary	Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition Score at Cycle 1	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.; The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration.; The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows.	baseline and cycle 1 (approximately 10 weeks)
Secondary	Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition (DR) Score at Cycle 4	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.; The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration.; The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows.	baseline and cycle 4 (approximately 22 weeks)
Secondary	Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition (DR) Score at Cycle 10	The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.; The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration.; The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows.	baseline and cycle 10 (approximately 46 weeks)