AzTrials
AzTrials

GlioblastomaPhase 3NCT00884741

Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma

A Phase 3 study testing 3-Dimensional Conformal Radiation Therapy, Bevacizumab and Intensity-Modulated Radiation Therapy in people with Glioblastoma and Gliosarcoma, run by National Cancer Institute (NCI) at 330 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized phase III trial studies temozolomide (TMZ) and radiation therapy (RT) to compare how well they work with or without bevacizumab in treating patients with newly diagnosed glioblastoma or gliosarcoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
3-Dimensional Conformal Radiation Therapy, Bevacizumab and Intensity-Modulated Radiation Therapy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
637 participants
Where
330 sitesin 3 countries
Study dates
15 Apr 2009to 17 Mar 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) confirmed by central review prior to step 2 registration
  • Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient size for analysis of O-6-methylguanine-DNA methyltransferase (MGMT) and determination of molecular profile
  • Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; at least 1 cubic centimeter of tissue composed primarily of tumor must be present
  • CUSA (Cavitron ultrasonic aspirator)-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged
  • Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis
  • The tumor tissue should be sent as soon as possible to maximize the likelihood of eligibility; tumor tissue should be submitted by 4 weeks after the surgical procedure so that the study registration and treatment can commence by the mandatory 5 week post-surgery outer limit
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  • Sites must submit tissue fir central review in order to obtain the MGMT analysis; patients from sites not following protocol-specified process for obtaining MGMT results will be made ineligible
  • The tumor must have a supratentorial component
  • History/physical examination within 14 days prior to step 2 registration
  • The patient must have recovered from the effects of surgery, postoperative infection, and other complications before step 2 registration
  • A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy; the postoperative scan must be performed within 28 days prior to step 1 registration
  • An MRI or computed tomography (CT) scan (potentially in addition to the postoperative scan) must be obtained within 10 days prior to the start of radiation therapy and must not demonstrate significant postoperative hemorrhage defined as > 1 cm diameter of blood; if > 1 cm of acute blood is detected, the patient will be ineligible for this trial; the radiation planning MRI or CT scan may be used to determine presence of hemorrhage
  • Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided pre- and postoperative contrast-enhanced CT scans are obtained and are of sufficient quality; preoperative and postoperative scans must be the same type; such patients cannot be enrolled into the advanced imaging component
  • Documentation of steroid doses within 14 days prior to step 2 registration
  • Karnofsky performance status >= 70
  • Absolute neutrophil count (ANC) >= 1,800 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 10.0 g/dL (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable)
  • Blood urea nitrogen (BUN) =< 30 mg/dL within 14 days prior to step 2 registration
  • Creatinine =< 1.7 mg/dl within 14 days prior to step 2 registration
  • Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg
  • Bilirubin =< 2.0 mg/dl within 14 days prior to step 2 registration
  • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x normal range within 14 days prior to step 2 registration
  • Systolic blood pressure =< 160 mg Hg or diastolic pressure =< 90 mm Hg within 14 days prior to step 2 registration
  • Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior to step 2 registration
  • Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to step 2 registration
  • Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW] heparin) must meet both of the following criteria:
  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of LMW heparin
  • Patient must provide study specific informed consent prior to study entry
  • Women of childbearing potential and male participants must practice adequate contraception
  • For females of child-bearing potential, negative serum pregnancy test within 14 days prior to step 2 registration

Who cannot join

  • 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)
  • Recurrent or multifocal malignant gliomas
  • Metastases detected below the tentorium or beyond the cranial vault
  • Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide or bevacizumab; prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
  • Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
  • Severe, active co-morbidity, defined as follows:
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  • Unstable angina and/or congestive heart failure within the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of step 2 registration
  • New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
  • History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
  • Serious and inadequately controlled cardiac arrhythmia
  • Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for tumor resection
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
  • 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
  • Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (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
  • 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
  • Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
  • Pregnant or lactating women
  • Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study
  • For American College of Radiology Imaging Network (ACRIN) 6686 Advanced Imaging: inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker)

Trial locations and contacts

330 sites in 3 countries.

306 sites in 3 countries

United States300 sites

  • Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • Summa Akron City Hospital/Cooper Cancer Center

    Akron, Ohio, 44304

  • Akron General Medical Center

    Akron, Ohio, 44307

  • New York Oncology Hematology PC - Albany

    Albany, New York, 12206

  • Lovelace Medical Center-Downtown

    Albuquerque, New Mexico, 87102

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87102

  • New Mexico Oncology Hematology Consultants

    Albuquerque, New Mexico, 87109

  • Inova Alexandria Hospital

    Alexandria, Virginia, 22304

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • McFarland Clinic PC-William R Bliss Cancer Center

    Ames, Iowa, 50010

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • Anne Arundel Medical Center

    Annapolis, Maryland, 21401

  • Langlade Hospital and Cancer Center

    Antigo, Wisconsin, 54409

  • Radiology Associates of Appleton/ThedaCare Regional Medical Center

    Appleton, Wisconsin, 54911

  • Texas Oncology-Arlington South

    Arlington, Texas, 76014

  • Northwest Community Hospital

    Arlington Heights, Illinois, 60005

  • Mission Hospital-Memorial Campus

    Asheville, North Carolina, 28801

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Sutter Cancer Centers Radiation Oncology Services-Auburn

    Auburn, California, 95603

  • Rocky Mountain Cancer Centers-Aurora

    Aurora, Colorado, 80012

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Saint Agnes Hospital

    Baltimore, Maryland, 21229

  • Summa Barberton Hospital

    Barberton, Ohio, 44203

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • UHHS-Chagrin Highlands Medical Center

    Beachwood, Ohio, 44122

  • UPMC-Heritage Valley Health System Beaver

    Beaver, Pennsylvania, 15009

  • Texas Oncology Bedford

    Bedford, Texas, 76022

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Sanford Clinic North-Bemidgi

    Bemidji, Minnesota, 56601

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Saint Luke's University Hospital-Bethlehem Campus

    Bethlehem, Pennsylvania, 18015

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • IU Health Bloomington

    Bloomington, Indiana, 47403

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Boulder Community Hospital

    Boulder, Colorado, 80301

  • Harrison Medical Center

    Bremerton, Washington, 98310

  • Saint Vincent's Medical Center

    Bridgeport, Connecticut, 06606

  • Maimonides Medical Center

    Brooklyn, New York, 11219

  • Saint Joseph Regional Cancer Center

    Bryan, Texas, 77802

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park

    Cameron Park, California, 95682

  • Sands Cancer Center

    Canandaigua, New York, 14424

  • Mercy Medical Center

    Canton, Ohio, 44708

  • Aultman Health Foundation

    Canton, Ohio, 44710

  • Cape Radiation Oncology

    Cape Girardeau, Missouri, 63703

  • Mercy San Juan Medical Center

    Carmichael, California, 95608

  • Physicians' Clinic of Iowa PC

    Cedar Rapids, Iowa, 52402

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Erlanger Medical Center

    Chattanooga, Tennessee, 37403

  • Northwestern University

    Chicago, Illinois, 60611

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • University of Cincinnati/Barrett Cancer Center

    Cincinnati, Ohio, 45219

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • John B Amos Cancer Center

    Columbus, Georgia, 31904

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Grant Medical Center

    Columbus, Ohio, 43215

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • John Muir Medical Center-Concord Campus

    Concord, California, 94520

  • Concord Hospital

    Concord, New Hampshire, 03301

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Texas Oncology Methodist Charlton Cancer Center

    Dallas, Texas, 75237

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Beaumont Hospital-Dearborn

    Dearborn, Michigan, 48124

  • Dekalb Medical Center

    Decatur, Georgia, 30033

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Texas Oncology-Denton South

    Denton, Texas, 76210

  • Porter Adventist Hospital

    Denver, Colorado, 80210

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Saint John Hospital and Medical Center

    Detroit, Michigan, 48236

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Saint Luke's Hospital of Duluth

    Duluth, Minnesota, 55805

  • Northeast Radiation Oncology Center

    Dunmore, Pennsylvania, 18512

  • Pocono Medical Center

    East Stroudsburg, Pennsylvania, 18301

  • Marshfield Clinic Cancer Center at Sacred Heart

    Eau Claire, Wisconsin, 54701

  • Sacred Heart Hospital

    Eau Claire, Wisconsin, 54701

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • The Regional Cancer Center

    Erie, Pennsylvania, 16505

  • Willamette Valley Cancer Center

    Eugene, Oregon, 97401

  • Saint Anne's Hospital

    Fall River, Massachusetts, 02721

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Genesys Regional Medical Center-West Flint Campus

    Flint, Michigan, 48532

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Radiation Oncology Associates PC

    Fort Wayne, Indiana, 46804

  • Parkview Hospital Randallia

    Fort Wayne, Indiana, 46805

  • The Klabzuba Cancer Center

    Fort Worth, Texas, 76104

  • California Cancer Center - North Fresno

    Fresno, California, 93720

  • Cancer Care Associates of Fresno Medical Group Inc

    Fresno, California, 93720

  • Saint Jude Medical Center

    Fullerton, California, 92835

  • Fox Chase Cancer Center Buckingham

    Furlong, Pennsylvania, 18925

  • Northeast Georgia Medical Center-Gainesville

    Gainesville, Georgia, 30501

  • University of Texas Medical Branch

    Galveston, Texas, 77555-0565

  • Adams Cancer Center

    Gettysburg, Pennsylvania, 17325

  • Bellin Memorial Hospital

    Green Bay, Wisconsin, 54301

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

  • UPMC Cancer Centers - Arnold Palmer Pavilion

    Greensburg, Pennsylvania, 15601

  • Cherry Tree Cancer Center

    Hanover, Pennsylvania, 17331

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Margaret R Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Cape Cod Hospital

    Hyannis, Massachusetts, 02601

  • IU Health Methodist Hospital

    Indianapolis, Indiana, 46202

  • Community Cancer Center East

    Indianapolis, Indiana, 46219

  • IU Health Central Indiana Cancer Centers-East

    Indianapolis, Indiana, 46219

  • Community Cancer Center North

    Indianapolis, Indiana, 46256

  • Saint Vincent Hospital and Health Care Center

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Jackson-Madison County General Hospital

    Jackson, Tennessee, 38301

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

  • Integrated Community Oncology Network-Southside Cancer Center

    Jacksonville, Florida, 32207

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Baptist Medical Center South

    Jacksonville, Florida, 32258

  • Integrated Community Oncology Network-Florida Cancer Center Beaches

    Jacksonville Beach, Florida, 32250

  • UW Cancer Center Johnson Creek

    Johnson Creek, Wisconsin, 53038

  • UPMC-Johnstown/John P. Murtha Regional Cancer Center

    Johnstown, Pennsylvania, 15901

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Truman Medical Center

    Kansas City, Missouri, 64108

  • The University of Kansas Cancer Center-South

    Kansas City, Missouri, 64131

  • The University of Kansas Cancer Center-North

    Kansas City, Missouri, 64154

  • CHI Health Good Samaritan

    Kearney, Nebraska, 68847

  • Armstrong Center for Medicine and Health

    Kittanning, Pennsylvania, 16201

  • Thompson Cancer Survival Center

    Knoxville, Tennessee, 37916

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Lancaster General Hospital

    Lancaster, Pennsylvania, 17604

  • Sparrow Hospital

    Lansing, Michigan, 48912

  • Nevada Cancer Research Foundation CCOP

    Las Vegas, Nevada, 89106

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Central Maine Medical Center

    Lewiston, Maine, 04240

  • Saint Elizabeth Regional Medical Center

    Lincoln, Nebraska, 68510

  • Rocky Mountain Cancer Centers-Littleton

    Littleton, Colorado, 80120

  • Saint Barnabas Medical Center

    Livingston, New Jersey, 07039

  • Monmouth Medical Center

    Long Branch, New Jersey, 07740

  • Texas Oncology-Longview Cancer Center

    Longview, Texas, 75601

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • The James Graham Brown Cancer Center at University of Louisville

    Louisville, Kentucky, 40202

  • Lowell General Hospital

    Lowell, Massachusetts, 01854

  • Covenant Medical Center-Lakeside

    Lubbock, Texas, 79410

  • Dean Hematology and Oncology Clinic

    Madison, Wisconsin, 53717

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Elliot Hospital

    Manchester, New Hampshire, 03103

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • Marshfield Medical Center

    Marshfield, Wisconsin, 54449

  • Mercy Medical Center - North Iowa

    Mason City, Iowa, 50401

  • Toledo Clinic Cancer Centers-Maumee

    Maumee, Ohio, 43537

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • UPMC Cancer Center at UPMC McKeesport

    McKeesport, Pennsylvania, 15132

  • Lake University Ireland Cancer Center

    Mentor, Ohio, 44060

  • Baptist Hospital of Miami

    Miami, Florida, 33176

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Southwest General Health Center Ireland Cancer Center

    Middleburg Heights, Ohio, 44130

  • Froedtert and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Marshfield Clinic-Minocqua Center

    Minocqua, Wisconsin, 54548

  • Providence Hospital

    Mobile, Alabama, 36608

  • Memorial Medical Center

    Modesto, California, 95355

  • Trinity Medical Center

    Moline, Illinois, 61265

  • Intercommunity Cancer Center

    Monroeville, Pennsylvania, 15146

  • IU Health Ball Memorial Hospital

    Muncie, Indiana, 47303

  • Intermountain Medical Center

    Murray, Utah, 84107

  • Edward Hospital/Cancer Center

    Naperville, Illinois, 60540

  • Allegheny Valley Hospital

    Natrona Heights, Pennsylvania, 15065

  • The Hospital of Central Connecticut

    New Britain, Connecticut, 06050

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • UPMC Jameson

    New Castle, Pennsylvania, 16105

  • Yale University

    New Haven, Connecticut, 06520

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • William Backus Hospital

    Norwich, Connecticut, 06360

  • Bay Area Tumor Institute

    Oakland, California, 94609

  • Kaiser Permanente Oakland-Broadway

    Oakland, California, 94611

  • South Nassau Communities

    Oceanside, New York, 11572

  • West Texas Cancer Center

    Odessa, Texas, 79761

  • McKay-Dee Hospital Center

    Ogden, Utah, 84403

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Alegent Health Immanuel Medical Center

    Omaha, Nebraska, 68122

  • Alegent Health Bergan Mercy Medical Center

    Omaha, Nebraska, 68124

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Saint Joseph Hospital - Orange

    Orange, California, 92868

  • 21st Century Oncology-Orange Park

    Orange Park, Florida, 32073

  • Saint Charles Hospital

    Oregon, Ohio, 43616

  • Florida Hospital Orlando

    Orlando, Florida, 32803

  • UF Cancer Center at Orlando Health

    Orlando, Florida, 32806

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • 21st Century Oncology-Palatka

    Palatka, Florida, 32177

  • Paoli Memorial Hospital

    Paoli, Pennsylvania, 19301

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • Singing River Hospital

    Pascagoula, Mississippi, 39581

  • Sacred Heart Hospital

    Pensacola, Florida, 32504

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61603

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Aria Health-Torresdale Campus

    Philadelphia, Pennsylvania, 19114

  • FirstHealth of the Carolinas-Moore Regional Hosiptal

    Pinehurst, North Carolina, 28374

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • UPMC-Shadyside Hospital

    Pittsburgh, Pennsylvania, 15232

  • UPMC Jefferson Regional Radiation Oncology

    Pittsburgh, Pennsylvania, 15236

  • UPMC-Passavant Hospital

    Pittsburgh, Pennsylvania, 15237

  • Pomona Valley Hospital Medical Center

    Pomona, California, 91767

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Naval Medical Center - Portsmouth

    Portsmouth, Virginia, 23708-2197

  • Hudson Valley Oncology Associates

    Poughkeepsie, New York, 12601

  • Kansas City NCI Community Oncology Research Program

    Prairie Village, Kansas, 66208

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Utah Valley Regional Medical Center

    Provo, Utah, 84604

  • Duke Women's Cancer Care Raleigh

    Raleigh, North Carolina, 27607

  • Kaiser Permanente-Rancho Cordova Cancer Center

    Rancho Cordova, California, 95670

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • Riverview Medical Center/Booker Cancer Center

    Red Bank, New Jersey, 07701

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Southern Regional Medical Center

    Riverdale, Georgia, 30274

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Highland Hospital

    Rochester, New York, 14620

  • University Radiation Oncology

    Rochester, New York, 14626

  • University of Rochester

    Rochester, New York, 14642

  • Rohnert Park Cancer Center

    Rohnert Park, California, 94928

  • Sutter Cancer Centers Radiation Oncology Services-Roseville

    Roseville, California, 95661

  • The Permanente Medical Group-Roseville Radiation Oncology

    Roseville, California, 95678

  • William Beaumont Hospital-Royal Oak

    Royal Oak, Michigan, 48073

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • Mercy General Hospital Radiation Oncology Center

    Sacramento, California, 95819

  • South Sacramento Cancer Center

    Sacramento, California, 95823

  • Saint Mary's of Michigan

    Saginaw, Michigan, 48601

  • Integrated Community Oncology Network-Flager Cancer Center

    Saint Augustine, Florida, 32086

  • Coborn Cancer Center at Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Cancer Care Center, Incorporated

    Salem, Ohio, 44460

  • Salem Hospital

    Salem, Oregon, 97301

  • Utah Cancer Specialists-Salt Lake City

    Salt Lake City, Utah, 84106

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • LDS Hospital

    Salt Lake City, Utah, 84143

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • University of California San Diego

    San Diego, California, 92103

  • California Pacific Medical Center-Pacific Campus

    San Francisco, California, 94115

  • North Coast Cancer Care

    Sandusky, Ohio, 44870

  • Kaiser Permanente Medical Center - Santa Clara

    Santa Clara, California, 95051

  • Memorial University Medical Center

    Savannah, Georgia, 31404

  • Maine Medical Center- Scarborough Campus

    Scarborough, Maine, 04074

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Arizona Oncology Services Foundation

    Scottsdale, Arizona, 85260

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122-4307

  • UPMC Cancer Center at UPMC Northwest

    Seneca, Pennsylvania, 16346

  • Texas Cancer Center-Sherman

    Sherman, Texas, 75090

  • Louisiana State University Health Sciences Center Shreveport

    Shreveport, Louisiana, 71103

  • Sanford Cancer Center-Oncology Clinic

    Sioux Falls, South Dakota, 57104

  • Northern Indiana Cancer Research Consortium

    South Bend, Indiana, 46628

  • Kaiser Permanente Cancer Treatment Center

    South San Francisco, California, 94080

  • Sparta Cancer Treatment Center

    Sparta, New Jersey, 07871

  • Spartanburg Medical Center

    Spartanburg, South Carolina, 29303

  • Cancer Care Northwest - Spokane South

    Spokane, Washington, 99202

  • Memorial Medical Center

    Springfield, Illinois, 62781

  • D'Amour Center for Cancer Care

    Springfield, Massachusetts, 01107

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Dixie Medical Center Regional Cancer Center

    St. George, Utah, 84770

  • Trinity's Tony Teramana Cancer Center

    Steubenville, Ohio, 43952

  • Saint Michael's Hospital

    Stevens Point, Wisconsin, 54481

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Robert and Carol Weissman Cancer Center at Martin Health

    Stuart, Florida, 34994

  • Texas Oncology Cancer Center Sugar Land

    Sugar Land, Texas, 77479

  • Flower Hospital

    Sylvania, Ohio, 43560

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467-2490

  • North Suburban Medical Center

    Thornton, Colorado, 80229

  • Mercy Saint Anne Hospital

    Toledo, Ohio, 43623

  • Arizona Oncology Associates-West Orange Grove

    Tucson, Arizona, 85704

  • Natalie Warren Bryant Cancer Center at Saint Francis

    Tulsa, Oklahoma, 74136

  • Tyler Cancer Center

    Tyler, Texas, 75702

Other trials in United States

Canada5 sites

  • Health Sciences North

    Greater Sudbury, Ontario, P3E 5J1

  • CHUM - Hopital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • McGill University Department of Oncology

    Montreal, Quebec, H2W 1S6

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Doctor H. Bliss Murphy Cancer Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

Other trials in Canada

Israel1 site

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 64239

Other trials in Israel

About this study

Official title: Phase III Double-blind Placebo-Controlled Trial of Conventional Concurrent Chemoradiation and Adjuvant Temozolomide Plus Bevacizumab Versus Conventional Concurrent Chemoradiation and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma

This randomized phase III trial studies temozolomide (TMZ) and radiation therapy (RT) to compare how well they work with or without bevacizumab in treating patients with newly diagnosed glioblastoma or gliosarcoma. 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may find tumor cells and help kill them. It is not yet known whether temozolomide and radiation therapy are more effective when given together with or without bevacizumab in treating glioblastoma or gliosarcoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine whether the addition of bevacizumab to temozolomide and radiation improves efficacy as measured by progression-free and/or overall survival.

II. To assess the association between overall survival and K^trans change from T1 to T2. (ACRIN 6686) III. To assess the association between overall survival and spin echo cerebral blood volume (CBV) change from T1 to T2. (ACRIN 6686)

SECONDARY OBJECTIVES:

  1. To determine whether the tumor molecular profile conferring a mesenchymal/angiogenic phenotype is associated with a selective increase in benefit, as measured by either overall survival or progression-free survival, from the addition of bevacizumab.

II. To compare and record the toxicities of the conventional and bevacizumab-containing regimens.

III. To assess the association between progression-free survival and K^trans change from T1 to T2. (ACRIN 6686) IV. To assess the association between progression-free survival and spin echo CBV change from T1 to T2. (ACRIN 6686) V. To assess the association between values of K^trans and spin echo CBV measured separately at T0 and at T1, and overall and progression-free survival. (ACRIN 6686) VI. To assess the association between overall survival and K^trans changes from T0 to T1 and from T2 to T3. (ACRIN 6686) VII. To assess the association between overall survival and spin echo CBV changes from T0 to T1 and from T2 to T3. (ACRIN 6686) VIII. To assess the association between overall survival and apparent diffusion coefficient (ADC) change from T0 to T1. (ACRIN 6686) IX. To assess the association between overall survival and ADC change from T1 to T2. (ACRIN 6686) X. To assess the association between progression-free survival and ADC change from T0 to T1. (ACRIN 6686) XI. To assess the association between progression-free survival and ADC change from T1 to T2. (ACRIN 6686) XII. To assess the association between T1 values of ADC and overall and progression-free survival. (ACRIN 6686) XIII. To assess the association between change in lesion size between T1 and T3, as measured by advanced magnetic resonance imaging (MRI), and overall and progression-free survival. (ACRIN 6686)

TERTIARY OBJECTIVES:

  1. To determine the differential acute effects associated with the addition of bevacizumab to temozolomide and radiation, as compared to the conventional arm, on measures of neurocognitive function, health-related quality of life, and symptoms during radiation and across the longitudinal progression-free interval.

II. To determine the relationship of neurocognitive function, health-related quality of life, and symptoms, with progression-free and overall survival.

III. To determine the association between tumor molecular profile (i.e., mesenchymal/angiogenic phenotype and proneural phenotype) and neurocognitive function, health-related quality of life, and symptoms.

IV. To describe the association between health-related quality of life as measured by the European Organization for Research and Treatment Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTC-QL30/BCM20) and mean symptom severity as measured by the M. D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) in patients enrolled in this study.

  1. To evaluate the relationship between self-reported neurocognitive function and objectively measured tests of neurocognitive function (NCF).

VI. To assess the association between measures of change in enhancing tumor size at week 22 and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab.

VII. To assess the association between measures of change in T2-based tumor size at week 22 and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab.

VIII. To assess the association between changes in ADC values and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab.

OUTLINE: Patients are randomized to 1 of 2 treatment arms (there are also two registration steps prior to randomization which are labeled as "arms" in ClinicalTrials.gov to facilitate entry of results into the website).

ARM I: Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide orally (PO) once daily (QD) for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.

ARM II: Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.

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

Being tested
3-Dimensional Conformal Radiation Therapy, Bevacizumab, Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis, Placebo
Medical subject headings
Glioblastoma, Gliosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 3-Dimensional Conformal Radiation TherapyRadiation

    Also called 3-dimensional radiation therapy, 3D CONFORMAL RADIATION THERAPY, 3D CRT, 3D-CRT

    Undergo 3-dimentional conformal radiation therapy

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

    Undergo intensity-modulated radiation therapy

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PlaceboOther

    Also called placebo therapy, PLCB, sham therapy

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • TemozolomideDrug

    Also called CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831

    Given orally

Study groups in NCT00884741
Study groupRoleWhat they receive
Arm I (radiation therapy, temozolomide, placebo)Active comparatorPatients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide PO QD for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.
Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Other: Placebo; Other: Quality-of-Life Assessment; Drug: Temozolomide
Arm II (radiation therapy, temozolomide, bevacizumab)ExperimentalPatients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.
Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Biological: Bevacizumab; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS)

    Survival time was defined as time from randomization to date of death from any cause and was estimated by the Kaplan-Meier method. Patients last known to be alive were censored at the date of last contact. This analysis was planned to occur when 390 deaths had been reported.

    Measured: From randomization to date of death or last follow-up. Analysis occurs after all 390 deaths have been reported.

  2. Progression-free Survival (PFS)

    Progression-free survival was defined as time from randomization to date of progression, death, or last follow-up, and was estimated by the Kaplan-Meier method. Patients last known to be alive were censored at the date of last contact. This analysis was planned to occur when 390 deaths had been reported.

    Measured: From randomization to date of progression, death, or last follow-up for progression-free survival. Analysis occurs after all 390 deaths have been reported.

Secondary outcomes (1)

  1. Incidence of Grade 3 and Higher Treatment-related Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 3.0

    AEs are graded by using CTCAE 3.0. The difference between the two randomized arms in the percentage of patients with grade 3 or higher toxicities reported as possibly/probably/definitely related to protocol treatment will be tested using a chi square test.

    Measured: Up to 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2009 (estimated)
  2. Study start15 Apr 2009
  3. Primary completion17 Mar 2013
  4. Study completion17 Mar 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
637 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00884741
Sponsor's protocol ID
NCI-2009-01670
Other IDs
NCI-2009-01670, RTOG-0825, RTOG 0825, CDR0000640428, RTOG-0825, RTOG-0825, U10CA180868, U10CA021661
Status last verified
Jul 2019
First submitted
18 Apr 2009
Last updated
24 Jul 2019
Data monitoring committee
No

Publications

  • Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. doi: 10.1056/NEJMoa1308573.

    PubMed 24552317

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 3-Dimensional Conformal Radiation Therapy, Bevacizumab and Intensity-Modulated Radiation Therapy in people with Glioblastoma and Gliosarcoma, run by National Cancer Institute (NCI) at 330 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 330 sites in United States, Canada, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: From randomization to date of death or last follow-up. Analysis occurs after all 390 deaths have been reported.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00884741, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2019.

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