Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Phase III Intergroup Study of Radiotherapy With Concomitant and Adjuvant Temozolomide Versus Radiotherapy With Adjuvant PCV Chemotherapy in Patients With 1p/19q Co-deleted Anaplastic Glioma or Low Grade Glioma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00887146
• Other study ID #: N0577
• Secondary ID: NCI-2011-01915EO
• Status: Recruiting
• Phase: Phase 3
• Start date: September 2009
• Est. completion date: October 2025

Study information

• Verified date: April 2024
• Source: Alliance for Clinical Trials in Oncology
• Contact: Kurt Jaeckle, MD
• Phone: 904-953-7102
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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. It is not yet known whether giving radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma.

Description:

This study will be a randomized phase III for patients with newly diagnosed co-deleted 1p/19q anaplastic glioma or high risk low grade glioma. The trial will only enroll patients with 1p/19q co-deletion. This study includes two arms as described in the "Arms" section. A dynamic allocation procedure will be used to allocate an equal number of patients to different arms (Arms A:B = 1:1). This procedure will balance the marginal distributions of the stratification factors among arms. The stratification factors that will be used are cooperative groups (EORTC vs. all North American groups), age (≤ 50 vs. > 50), performance score (ECOG 0-1 vs. 2), and tumor grade (anaplastic glioma vs. low grade glioma). The primary goal is to determine whether patients who receive radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant temozolomide (RT + TMZ --> TMZ) (Arm B) have a marginally better progression free survival (PFS) as compared with patients who receive radiotherapy followed by PCV chemotherapy (RT --> PCV)(Arm A). Secondary Goals: 1. Time to Progression - To determine whether patients who receive (RT + TMZ --> TMZ) have a significantly longer time to progression (clinical or radiographic progression) as compared with patients who receive radiotherapy followed by adjuvant PCV chemotherapy (RT --> PCV). 2. Correlation between exploratory biomarkers and survival - To determine whether there is a difference in survival based on t(1;19)(q10, p10) translocation status and MGMT promoter hypermethylation status. 3. Descriptive Comparisons of Additional Secondary Endpoints - To perform descriptive comparisons of additional secondary outcome endpoints, including overall survival, objective tumor response, prognostic factor analysis and quality of life. 4. Toxicity - To determine the toxicity of the treatment in each arm and perform descriptive comparisons. 5. Neurocognitive and Quality of Life (QOL) Effects - To determine the neurocognitive and QOL effects in patients treated on this protocol and correlate these results with outcome endpoints. 6. Banking of Biospecimens and Neuroimaging Studies - To store blood products (i.e., plasma, DNA and buffy coat), tumor tissue and MRI/CT images for future scientific investigations. After completion of study treatment, patients are followed every 12 weeks for 1 year, then every 4 months for 2 years and then every 6 months until progressive disease or until the end of study participation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: October 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Pre-Registration Inclusion Criteria:

• United States (US) and Canadian sites:
• This review is mandatory prior to registration to confirm eligibility; patients must be willing to submit tissue samples for mandatory central pathology review submission; it should be initiated as soon after surgery as possible
• Tissue must have been determined to have local 1p/9q co-deletion and IDH mutation prior to submission for central path review
• Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility, the 1p/19q analysis results will be accepted from the local site, as determined by either a locally available or reference laboratory (for US, must be Clinical Laboratory Improvement Act [CLIA] certified); acceptable methods for determination of 1p/19q loss include fluorescent in-situ hybridization (FISH), by genomic sequencing or methylomic analyses; US and Canadian sites must send a copy of the official report to the pathology coordinator and quality assurance specialist (QAS)
• Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic analyses; this should be performed at the local site (US: performed in a CLIA certified laboratory); the site must send a copy of the official report to the pathology coordinator and QAS

Registration Inclusion Criteria:

• Newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligible if they have had a prior surgical procedure > 3 months earlier for low grade glioma, as long as the patient has not received prior radiation or prior chemotherapy
• Histological evidence of World Health Organization (WHO) grade III anaplastic glioma or WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and the presence of an either IDH1 or IDH2, both as established by a local or referenced laboratory qualified for the study
• Note: mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q
• Patients with codeleted low grade gliomas must also be considered "high risk" by

exhibiting one or more of the following characteristics:

• Age >= 40 and any surgical therapy
• Age < 40 with prior and subtotal resection or biopsy (i.e., anything less than gross total resection)
• Documented growth following prior surgery (NOTE: patients with prior surgery cannot have received prior radiation, chemotherapy or targeted therapy)
• Intractable seizures
• Surgery (partial or gross total resection or biopsy) must be performed >= 2 weeks prior to registration; patient must have recovered adequately from the effects of surgery
• Absolute neutrophil count (ANC) >= 1,500/mm^3 obtained =< 21 days prior to registration
• Platelet (PLTs) count >= 100,000/mm^3 obtained =< 21 days prior to registration
• Hemoglobin (Hgb) > 9.0 g/dL obtained =< 21 days prior to registration
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) obtained =< 21 days prior to registration
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN obtained =< 21 days prior to registration
• Creatinine =< 1.5 x ULN obtained =< 21 days prior to registration
• Negative serum or urine pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• Willingness and ability to personally complete neurocognitive testing (without assistance) and willingness to complete the QOL testing, (either personally or with assistance)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
• Written informed consent
• Willingness to return to enrolling institution for follow-up during the active monitoring phase (that is, the active treatment and observation portion) of the study); patients who have been formally transferred to another active and approved site participating in this study would not need to return to the enrolling institution for this purpose
• Willingness to allow the provision of tissue samples for correlative research, as long as adequate tissues are available; patients will not be excluded from participation in the study, if they are willing to allow provision of tissues for the correlative research, but there are insufficient quantities of tissue for the correlative analyses (e.g., a patient otherwise eligible and willing who had biopsy only) Willingness to allow the provision of blood samples for correlative research; patients are not excluded from participation in the study, if they are willing to provide the mandatory biospecimens for translational/correlative research, but for logistical reasons the specimens(s) were not obtainable or if the volume collected was insufficient

Registration Exclusion Criteria:

• The following categories are ineligible:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception or contraceptive method during this study and 6 months following the completion of chemotherapy treatments
• History of prior radiation therapy or chemotherapy for glioma; note: patients who have a history of prior low grade glioma (with or without a distant history of prior surgery for that glioma), but who have never received prior chemotherapy or radiation therapy for the glioma are eligible for the study
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Concomitant serious immunocompromised status (other than that related to concomitant steroids) that would compromise the safety of the patient on the study
• Patients known to be human immunodeficiency virus (HIV) positive and currently receiving retroviral therapy are not eligible; note: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
• Other active malignancy within 5 years of registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, the patient is not eligible if they are receiving other specific treatment (with the exclusion of hormonal therapy or Her-2 inhibitors) for their cancer or if they have received prior total body irradiation which included the brain
• History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Recent history of hepatitis infection or if the treating physician determined that the patient would be at significant risk of reactivation of hepatitis

Related Conditions & MeSH terms

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

Intervention

Drug:
• concomitant temozolomide (TMZ)
75 mg/m^2, orally daily

Radiation:
• radiotherapy

Drug:
• procarbazine
Days 8-21: 60 mg/m^2 orally
• adjuvant temozolomide (TMZ)
150 or 200 mg/m^2 orally
• CCNU
Day 1: 110 mg/m^2 orally
• vincristine
Days 8 and 29: 1.4 mg/m^2 IV

Locations

Country	Name	City	State
Austria	Medical University Vienna	Vienna
Belgium	Alegemeen Ziekenhuis Middelheim	Antwerpen
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
France	Centre Leon Berard	Lyon
France	Centre Antoine Lacassagne	Nice
France	Gustave Roussy	Villejuif
Netherlands	Academ Zienkenhuis Bij De University	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Maastro Clinic-Maastricht Radiation Oncology	Maastricht
Netherlands	Erasmus University Medical Center	Rotterdam
United States	Jefferson Abington Hospital	Abington	Pennsylvania
United States	Bixby Medical Center	Adrian	Michigan
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	Emory Proton Therapy Center	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	The Medical Center of Aurora	Aurora	Colorado
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Community Cancer Institute	Clovis	California
United States	University Oncology Associates	Clovis	California
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Greater Regional Medical Center	Creston	Iowa
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Saint Luke's Hospital-Anderson Campus	Easton	Pennsylvania
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Unity Hospital	Fridley	Minnesota
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	University of Texas Medical Branch	Galveston	Texas
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Tri-Cities Cancer Center	Kennewick	Washington
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	AMITA Health Adventist Medical Center	La Grange	Illinois
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Nebraska Hematology and Oncology	Lincoln	Nebraska
United States	Southeast Nebraska Cancer Center - 68th Street Place	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Norton Brownsboro Hospital and Medical Campus	Louisville	Kentucky
United States	Norton Hospital Pavilion and Medical Campus	Louisville	Kentucky
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	West Jefferson Medical Center	Marrero	Louisiana
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana
United States	Providence Hospital	Mobile	Alabama
United States	Memorial Medical Center	Modesto	California
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Skagit Regional Health Cancer Care Center	Mount Vernon	Washington
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Intermountain Medical Center	Murray	Utah
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Nebraska Cancer Specialists - Omaha	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Kaiser Permanente-Ontario	Ontario	California
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Arizona Oncology-Deer Valley Center	Phoenix	Arizona
United States	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Highland Hospital	Rochester	New York
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Cancer Trials Support Unit	Rockville	Maryland
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint George Regional Medical Center	Saint George	Utah
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Maine Medical Partners Neurology	Scarborough	Maine
United States	Regional West Medical Center Cancer Center	Scottsbluff	Nebraska
United States	Arizona Oncology Services Foundation	Scottsdale	Arizona
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	VCU Community Memorial Health Center	South Hill	Virginia
United States	Maine Medical Partners - South Portland	South Portland	Maine
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Memorial Medical Center	Springfield	Illinois
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Overlook Hospital	Summit	New Jersey
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Munson Medical Center	Traverse City	Michigan
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	University of Michigan Health - West	Wyoming	Michigan

Sponsors (4)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	Canadian Cancer Trials Group, European Organisation for Research and Treatment Center (EORTC), National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	The distribution of progression free survival for Arms A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median progression free survival (PFS) will be estimated with their confidence intervals. The Cox proportional hazards model will be used to assess whether the distributions of progression survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and performance score). Both non-inferiority and superiority will be tested in this trial for the primary goal and no multiple-comparison adjustment will be considered.	Time from study registration to time of tumor progression or death due to any cause, whichever comes first, assessed up to 16 years
Secondary	Time to progression	Estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors. Correlations among baseline neurocognitive test scores and progression free survival will be analyzed using Cox proportional hazards model.	Time from study registration to the earliest evidence of clinical progression, radiographic progression or neurocognitive progression, assessed up to 16 years
Secondary	Time to neurocognitive progression, assessed using the Hopkins Verbal Learning Test-Revised for Free Recall, Delayed Recall, and Delayed Recognition; the Controlled Oral Word Association test; and the Trail Making Test Part A or B	Estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors. For each test in the battery, a standard error of measurement will be used to derive the Reliable Change Index (RCI) which will be used to represent the 90% confidence interval for the difference in raw scores from baseline to follow-up assessment will be coded as 1 (deterioration), 2 (no change), and 3 (improved) according to the RCI.	Time from study registration to the first cognitive failure, assessed up to 16 years
Secondary	Overall survival	The Cox proportional hazards model will be used to assess whether the distributions of overall survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and Performance Score). The distribution of overall survival for Arm A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median survivals will be estimated with their 95% confidence intervals.	Time from study registration to time of death due to any cause, assessed up to 16 years
Secondary	Objective tumor response defined as a complete response or partial response	Summarized for each arm and compared between the arms using the Chi square test.	Up to 16 years
Secondary	Treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0	The maximum grade for each type of treatment-related adverse event will be recorded for each patient, and frequency tables for each arm will be reviewed to determine patterns. In addition, will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. Adverse events and treatment-related adverse events will be evaluated using all patients. Treatment-related adverse events will be tabulated for each arm.	Up to 16 years

External Links

•   Clinical trial summary from the National Cancer Institute's PDQ® database