Temozolomide With or Without Veliparib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Glioblastoma Clinical Trial

Official title:

A Phase II/III Randomized Trial of Veliparib or Placebo in Combination With Adjuvant Temozolomide in Newly Diagnosed Glioblastoma With MGMT Promoter Hypermethylation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02152982
• Other study ID #: NCI-2014-00616
• Secondary ID: NCI-2014-00616A0
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: December 15, 2014
• Est. completion date: December 15, 2024

Study information

• Verified date: April 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II/III trial studies how well temozolomide and veliparib work compared to temozolomide alone in treating patients with newly diagnosed glioblastoma multiforme. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether temozolomide is more effective with or without veliparib in treating glioblastoma multiforme.

Description:

PRIMARY OBJECTIVE:

I. Test whether the experimental combination of ABT-888 (veliparib) combined with TMZ (temozolomide), compared to the control of placebo combined with TMZ, significantly extends overall survival in newly diagnosed glioblastoma multiforme (GBM) patients with tumor MGMT promoter hypermethylation.

SECONDARY OBJECTIVES:

I. Test whether the experimental treatment significantly extends progression-free survival.

II. Test whether the experimental treatment improves objective tumor response. III. Test whether the experimental treatment is associated with significantly greater rates of grade 3 or higher adverse events.

CORRELATIVE SCIENCE OBJECTIVES:

I. Evaluate the utility of dynamic susceptibility contrast (DSC) and diffusion weighted imaging (DWI) magnetic resonance imaging (MRI) techniques in defining time to progression in the setting of a large multi-institutional clinical trial.

II. Test the concordance between site-determined MGMT methylation status and central laboratory determination of MGMT status in cases with local testing.

III. Evaluate whether genetic or epigenetic alterations in deoxyribonucleic acid (DNA) repair or replication genes are associated with overall survival, progression-free survival, and objective tumor response.

IV. Test whether polymorphisms in MGMT, PARP1, or other DNA repair proteins, are associated with overall survival, progression-free survival, objective tumor response, or rates of grade 3 or higher adverse events.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5 and veliparib PO twice daily (BID) on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.

ARM II: Patients receive temozolomide as in Arm I and placebo PO BID on days 1-7. Treatment repeats every 28 days for 6 cycles in the absence of disease progression (confirmed progression) or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years, every 6 months for 2 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 447
• Est. completion date: December 15, 2024
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologic documentation: newly diagnosed World Health Organization (WHO) grade IV intracranial glioblastoma or gliosarcoma; GBM with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q codeleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q codeletion status

• Sufficient tissue available for central pathology review and MGMT methylation status evaluation

• Patients who have had a local MGMT testing that is unmethylated are not allowed to participate

• Tumor MGMT promoter hypermethylation determined by central testing at MD Anderson

• Confirmation by central pathology review of WHO grade IV glioblastoma or gliosarcoma

• Absolute neutrophil count (ANC) >= 1500 cells/mm^3 (within 14 days prior to study registration)

• Platelets >= 100,000 cells/mm^3 (within 14 days prior to study registration)

• Creatinine =< 1.5 x upper limit of normal (ULN) (within 14 days prior to study registration)

• Bilirubin =< 1.5 x ULN (within 14 days prior to study registration; unless patient has Gilbert's disease)

• Alanine aminotransferase (ALT) =< 3 x ULN (within 14 days prior to study registration)

• Aspartate aminotransferase (AST) =< 3 x ULN (within 14 days prior to study registration)

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Measurable disease or non-measurable disease; extent of resection: patients with complete resection, partial resection, or biopsy are eligible

• Progression: patients deemed to have progressive disease based on clinical deterioration after chemoradiation or radiographic progression outside of the radiation field are not eligible; patients deemed to have pseudoprogression are eligible

• Prior treatment:

• Must have completed standard radiotherapy and concomitant TMZ therapy as defined and determined by the study oncologist

• Besides concomitant TMZ with radiation, no other therapy (neo-adjuvant or adjuvant) can be given prior to study registration, including chemotherapy (also including Gliadel/carmustine [BCNU] wafers), biologics, immunotherapy, radiation therapy; the only exception is the Optune device (NovoTTF-100A), which may be started any time after end of radiation therapy up through the initiation of Cycle 1; intent to use Optune must be declared at registration for stratification

• No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation

• Not pregnant and not nursing; females of childbearing potential must have negative urine or serum pregnancy test within 7 days of registration but before start of treatment; a female of childbearing potential is a sexually mature female who:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

• Concomitant medications: patients receiving anticoagulation should be on stable dose 2 weeks prior to registration

• Comorbid conditions: patients are unable to participate due to the following:

• Generalized or partial seizure disorder that is uncontrolled at the time of registration; the definition of controlled generalized seizures is patients must be on a stable dose of anti-seizure medication and without generalized seizures for at least 10 days prior to registration; the definition of controlled partial seizures is patients must be on a stable dose of anti-seizure medication for at least 10 days prior to registration; patients with occasional breakthrough partial seizures are allowed at treating physician's discretion

• Grade 3 or 4 thromboembolic disease within 6 months (mo) of registration

• Known history of prolonged QT syndrome

• No history of major surgery =< 14 days prior to registration

• Patients must have adequate organ and marrow function measured within 28 days prior to administration of ABT-888 as defined below:

• >= 10.0 g/dL hemoglobin (Hb) with no blood transfusion in the past 28 days

• No Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS) or with features suggestive of AML/MDS

Related Conditions & MeSH terms

• Glioblastoma
• Gliosarcoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Placebo Administration
Given PO
• Quality-of-Life Assessment
Ancillary studies

Drug:
• Temozolomide
Given PO
• Veliparib
Given PO

Locations

Country	Name	City	State
Puerto Rico	Fundacion De Investigacion de Diego	San Juan
United States	Avera Cancer Institute-Aberdeen	Aberdeen	South Dakota
United States	Jefferson Abington Hospital	Abington	Pennsylvania
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Luminis Health Anne Arundel Medical Center	Annapolis	Maryland
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Mission Hospital	Asheville	North Carolina
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	The NeuroMedical Center-Clinic	Baton Rouge	Louisiana
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	OSF Saint Joseph Medical Center	Bloomington	Illinois
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Cleveland Clinic Mercy Hospital	Canton	Ohio
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Bon Secours Saint Francis Hospital	Charleston	South Carolina
United States	Charleston Oncology - Roper	Charleston	South Carolina
United States	Charleston Oncology - Saint Francis	Charleston	South Carolina
United States	Lowcountry Hematology Oncology PA-North Charleston	Charleston	South Carolina
United States	Lowcountry Hematology Oncology PA-West Ashley	Charleston	South Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Roper Hospital	Charleston	South Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Grant Medical Center	Columbus	Ohio
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	John Muir Medical Center-Concord	Concord	California
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Mary Imogene Bassett Hospital	Cooperstown	New York
United States	Baptist Health Corbin	Corbin	Kentucky
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Danville Regional Medical Center	Danville	Virginia
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Kaiser Permanente-Franklin	Denver	Colorado
United States	Iowa Methodist Medical Center	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	Ascension Saint John Hospital	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	John F Kennedy Medical Center	Edison	New Jersey
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Swedish Medical Center	Englewood	Colorado
United States	OSF Saint Francis Hospital and Medical Group	Escanaba	Michigan
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Simonds-Sinon Regional Cancer Center	Fitchburg	Massachusetts
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Fresno Cancer Center	Fresno	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Saint Jude Medical Center	Fullerton	California
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	East Carolina University	Greenville	North Carolina
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 Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Hartford Hospital	Hartford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	ECU Health Oncology Kinston	Kinston	North Carolina
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Kaiser Permanente-Rock Creek	Lafayette	Colorado
United States	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Baptist Health Lexington	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Kaiser Permanente-Lone Tree	Lone Tree	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Banner McKee Medical Center	Loveland	Colorado
United States	Lowell General Hospital	Lowell	Massachusetts
United States	University of Wisconsin Carbone Cancer Center - University Hospital	Madison	Wisconsin
United States	Baptist Health Madisonville/Merle Mahr Cancer Center	Madisonville	Kentucky
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Marshfield Medical Center	Marshfield	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Midstate Medical Center	Meriden	Connecticut
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Kaiser Permanente-Modesto	Modesto	California
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Lowcountry Hematology Oncology PA-Mount Pleasant	Mount Pleasant	South Carolina
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	The Hospital of Central Connecticut	New Britain	Connecticut
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	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Mount Sinai Hospital	New York	New York
United States	USC Norris Oncology/Hematology-Newport Beach	Newport Beach	California
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Faith Regional Health Services Carson Cancer Center	Norfolk	Nebraska
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	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	Creighton University Medical Center	Omaha	Nebraska
United States	Nebraska Cancer Specialists - Omaha	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Joseph Hospital - Orange	Orange	California
United States	Saint Charles Hospital	Oregon	Ohio
United States	AdventHealth Orlando	Orlando	Florida
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Menorah Medical Center	Overland Park	Kansas
United States	Baptist Health Paducah	Paducah	Kentucky
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	The Valley Hospital - Luckow Pavilion	Paramus	New Jersey
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Memorial Hospital West	Pembroke Pines	Florida
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	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Portsmouth Regional Hospital	Portsmouth	New Hampshire
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Rhode Island Hospital	Providence	Rhode Island
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Northwest Hospital Center	Randallstown	Maryland
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	Renown Regional Medical Center	Reno	Nevada
United States	Lakeview Medical Center-Marshfield Clinic	Rice Lake	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	Valley Health System Ridgewood Campus	Ridgewood	New Jersey
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Corewell Health Lakeland Hospitals - Saint Joseph Hospital	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	TidalHealth Peninsula Regional	Salisbury	Maryland
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	UC San Diego Medical Center - Hillcrest	San Diego	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	UCSF Medical Center-Parnassus	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Maine Center for Cancer Medicine-Scarborough	Scarborough	Maine
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Aurora Medical Center in Summit	Summit	Wisconsin
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	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Maine Center for Cancer Medicine-Topsham	Topsham	Maine
United States	Munson Medical Center	Traverse City	Michigan
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Northbay Cancer Center	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	John Muir Medical Center-Walnut Creek	Walnut Creek	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Valley Health System-Hematology/Oncology	Westwood	New Jersey
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	UPMC Susquehanna	Williamsport	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	University of Michigan Health - West	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Quality of Life (QOL)	Measured by the fatigue/uniscale tool. The fatigue/uniscale tool will be used as a measure of QOL. Potential differences in fatigue levels of patients treated on the two different arms will be evaluated. Changes in this measure will be evaluated over the course of treatment for both arms and will be compared using a two-sample t-test at each timepoint. Will also compute a normalized area under the curve (AUC) for the values of each patient over time and compare the mean AUCs for patients on the two arms.	Baseline to up to 5 years
Other	MGMT Status	The concordance between site-determined MGMT methylation status and central laboratory determination of MGMT status will be analyzed using the Chi-Square test of proportions and 95% confidence intervals for the proportion of tests in disagreement with the local site.	Baseline
Primary	Overall Survival (OS)	The distribution of OS for each arm will be estimated using the Kaplan-Meier method and compared with a stratified logrank test.	83 months
Secondary	Interaction With Optune Device	Cox proportional hazards model will be used to evaluate whether there is a potential interaction between the treatment arm and the Optune device. If an interaction is detected, separate analyses of treatment effect (using Cox models) will be done for patients treated with the Optune device and patients who were not treated with the Optune device.	5 years
Secondary	Progression-free Survival (PFS)	The distribution of PFS for each arm will be estimated using the Kaplan-Meier method, and be compared using Cox proportional hazard models with all stratification factors adjusted. Progression (PD): Defined by any of the following: > 25% increase in sum of products of perpendicular diameters of enhancing lesions, compared with the smallest tumor measurement obtained either at baseline or best response; Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after therapy initiation (stable doses of steroids include patient not on steroids) not caused by comorbid events; Any new lesion; Clear clinical deterioration not attributable to other causes apart from tumor or change in corticosteroid dose; Failure to return for evaluation as a result of death or deteriorating condition; Clear progression of non-measurable disease	83 months
Secondary	Objective Tumor Response	Defined as complete response (CR) or partial response (PR) as specified in the Revised Assessment in Neuro-Oncology criteria. An objective tumor response will be evaluated for each patient and the tumor response count will be summarized for each arm and compared using the Chi-square test. For CR, all of the following must be true: disappearance of all enhancing measurable and non-measurable disease; no new enhancing lesions; stable or improved non-enhancing lesions; patients must be off corticosteroids; stable or improved clinically; A PR requires all of the following: > 50% decrease in sum of products of perpendicular diameters of all measurable enhancing lesions compared with baseline; no progression of non-measurable disease; no new lesions; stable or improved non-enhancing lesions on same or lower dose of corticosteroids compared with baseline scan; steroid dose should be same or lower compared with baseline scan; stable or improved clinically	5 years
Secondary	Overall Adverse Event Rates for Grade 3 or Higher Adverse Events	Assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5 beginning April 1, 2018). The overall adverse event rates for grade 3 or higher adverse events will be summarized and be compared using Chi-Square or Fisher's Exact tests between treatment arms. 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. Treatment-related adverse events will be tabulated for each arm.	5 years