AzTrials
AzTrials

Giant Cell GlioblastomaPhase 2NCT01609790

Bevacizumab With or Without Trebananib in Treating Patients With Recurrent Brain Tumors

A Phase 2 study testing Bevacizumab, Laboratory Biomarker Analysis and Pharmacological Study in people with Giant Cell Glioblastoma and Glioblastoma, run by National Cancer Institute (NCI) at 244 sites in 2 countries.

Completed

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

Official record
Search all trials

Trial summary

This partially randomized phase II trial with a safety run-in component studies the side effects and how well bevacizumab given with or without trebananib works in treating patients with brain tumors that have come back (recurrent). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Giant Cell Glioblastoma, Glioblastoma, Gliosarcoma
What is being tested?
Bevacizumab, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
137 participants
Where
244 sitesin 2 countries
Study dates
4 Jun 2012to 20 May 2022
Phase
Phase 2
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 variants (gliosarcoma, glioblastoma with oligodendroglial features, giant cell glioblastoma); patients will be eligible if the original histology was a lower grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made
  • The tumor must be supratentorial; patients with infratentorial disease, spinal cord disease, and/or leptomeningeal disease are excluded
  • Patients must have shown unequivocal evidence for tumor progression on the previous treatment regimen (prior to enrollment on this study) by magnetic resonance imaging (MRI) scan of the brain with and without contrast within 14 days prior to registration; the dose of steroids must be stable or decreasing for at least 5 days prior to the scan; patients with tumor progression who then undergo surgical resection prior to enrollment on study may be eligible as long as pathology confirms progressive or recurrent glioblastoma multiforme (GBM) (or variants); for patients who undergo surgical resection, registration on study may not occur any sooner than 28 days from surgery; an MRI scan of the brain with and without contrast is still required within 14 days prior to registration on study but is not required to demonstrate measurable disease or tumor progression after surgery
  • Patients unable to undergo MRI because of non-compatible devices can be enrolled, provided computed tomography (CT) scans are obtained and are of sufficient quality; patients without non-compatible devices may not have CT scans performed to meet this requirement
  • History/physical examination within 14 days prior to registration
  • Karnofsky performance scale >= 70 within 14 days prior to registration
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  • Patients who have received prior treatment with interstitial brachytherapy, stereotactic radiosurgery, or implanted chemotherapy sources, such as wafers of polifeprosan 20 with carmustine, must have confirmation of progressive disease within 14 days prior to registration based upon nuclear imaging, magnetic resonance (MR) spectroscopy, perfusion imaging, or histopathology
  • Leukocytes > 3,000/mm^3 (within 14 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 14 days prior to registration)
  • Hemoglobin >= 10.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dL is acceptable) (within 14 days prior to registration)
  • Platelets >= 100,000 cells/mm^3 (within 14 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal (within 14 days prior to registration)
  • Bilirubin =< 2.0 mg/dL (within 14 days prior to registration)
  • Creatinine within normal upper institutional limits or creatinine clearance > 60 mL/min/1.73 m^2 (per 24 hour urine collection or calculated according to the Cockcroft-Gault formula) for subjects with creatinine levels above the institutional normal (within 14 days prior to registration)
  • Patients with creatinine levels below normal institutional limits are eligible
  • Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 (within 14 days prior to registration)
  • Urinary protein =< 30 mg/dL in urinalysis or =< 1+ on dipstick (within 14 days prior to registration)
  • Generally well-controlled blood pressure with systolic blood pressure =< 140 mm Hg AND diastolic blood pressure =< 90 mm Hg within 5 days prior to registration; the use of anti-hypertensive medications to control hypertension is permitted
  • Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (HCG) pregnancy test within 14 days prior to registration
  • Women of childbearing potential and male patients who are sexually active must practice adequate contraception during therapy and for 180 days (6 months) afterwards
  • Patient must provide study specific informed consent prior to study entry

Who cannot join

  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Prior systemic cytotoxic chemotherapy within (i.e., =<) 28 days (42 days for nitrosoureas or mitomycin C) prior to registration, or patients who have not returned to baseline or =< Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v. 4) grade 2 from adverse events (excluding alopecia) due to agents administered more than 28 days prior to registration
  • Patients who received non-cytotoxic drug therapy must be off treatment for at least 14 days prior to registration; prior treatment with anti-vascular endothelial growth factor (VEGF) targeted agents; AMG 386 therapy; or other molecules that inhibit angiopoietins or TEK tyrosine kinase, endothelial (Tie2) receptor including, but not limited to, XL-820, XL-184 (cabozantinib-s-malate), and CVX-060/PF-4856884 is not allowed regardless of time frame
  • Patients who have not yet completed at least 21 days (30 days for prior monoclonal antibody therapy) since ending other investigational device or drug trials, or who are currently receiving other investigational treatments
  • Treatment within 30 days prior to enrollment with strong immune modulators, including but not limited to systemic cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide, lenalidomide, and targeted immune modulators such as abatacept (CTLA-4-Ig), adalimumab, alefacept, anakinra, belatacept (LEA29Y), efalizumab, etanercept, infliximab, or rituximab
  • Prior radiotherapy within 90 days (3 months) prior to registration unless there is either: a) histopathologic confirmation of recurrent tumor; or b) new enhancement on MRI outside of the radiation treatment field
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  • Major surgical procedure (including craniotomy and open brain biopsy) or significant traumatic injury within 28 days prior to registration or those patients who receive a non-central nervous system (CNS) minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 3 days prior to registration; there is no waiting period for central line placement; there is a 7-day window for recovery prior to registration for patients who underwent stereotactic biopsy of the brain
  • Prior therapy with anti-VEGF targeted agents (e.g. bevacizumab, cediranib, vandetanib, aflibercept, sunitinib, sorafenib, etc.); prior therapy with thalidomide and lenalidomide is allowed as long as treatment has not occurred within 30 days prior to enrollment
  • More than 2 relapses
  • Therapeutic anticoagulation with warfarin < 7 days prior to registration; (therapeutic or prophylactic therapy with aspirin, a low-molecular weight heparin, or a Factor Xa inhibitor is acceptable)
  • Intratumoral hemorrhage or peritumoral hemorrhage, demonstrated by MRI or CT scan, CTCAE, v. 4 grade 2 or greater or evidence of significant hemorrhage (regardless of CTCAE, v. 4 grade) defined as > 1 cm diameter of blood (including postoperative hemorrhage)
  • Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE, v. 4 grade 3 or greater within 30 days prior to study entry
  • Severe, active co-morbidity, defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within 180 days (6 months) prior to registration
  • Transmural myocardial infarction within 180 days (6 months) prior to registration
  • History of stroke, cerebral vascular accident (CVA), or transient ischemic attack within 180 days (6 months) prior to registration
  • 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 registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
  • Known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhages in the past
  • History of non-healing wounds or ulcers, or bone fractures within 90 days (3 months) prior to registration
  • History of venous or arterial thromboembolism within 12 months prior to registration
  • Prior allergic reaction to the study drugs involved in this study

Trial locations and contacts

244 sites in 2 countries.

244 sites in 2 countries

United States243 sites

  • Summa Health System - Akron Campus

    Akron, Ohio, 44304

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • New York Oncology Hematology PC - Albany

    Albany, New York, 12206

  • New York Oncology Hematology PC - Albany Medical Center

    Albany, New York, 12208

  • American Fork Hospital / Huntsman Intermountain Cancer Center

    American Fork, Utah, 84003

  • Alaska Breast Care and Surgery LLC

    Anchorage, Alaska, 99508

  • Alaska Women's Cancer Care

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • Michigan Cancer Research Consortium NCORP

    Ann Arbor, Michigan, 48106

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • Langlade Hospital and Cancer Center

    Antigo, Wisconsin, 54409

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Mountain Radiation Oncology PA

    Asheville, North Carolina, 28801

  • AdventHealth Infusion Center Asheville

    Asheville, North Carolina, 28803

  • Messino Cancer Centers

    Asheville, North Carolina, 28806

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Hematology Oncology Associates of Central New York-Auburn

    Auburn, New York, 13021

  • Rush - Copley Medical Center

    Aurora, Illinois, 60504

  • Texas Oncology-Austin Midtown

    Austin, Texas, 78705

  • Texas Oncology - Central Austin Cancer Center

    Austin, Texas, 78731

  • Texas Oncology - South Austin Cancer Center

    Austin, Texas, 78745

  • Summa Health System - Barberton Campus

    Barberton, Ohio, 44203

  • UPMC-Heritage Valley Health System Beaver

    Beaver, Pennsylvania, 15009

  • Texas Oncology Bedford

    Bedford, Texas, 76022

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Saint Luke's University Hospital-Bethlehem Campus

    Bethlehem, Pennsylvania, 18015

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Sandra L Maxwell Cancer Center

    Cedar City, Utah, 84720

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Columbus Oncology and Hematology Associates Inc

    Columbus, Ohio, 43214

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Columbus NCI Community Oncology Research Program

    Columbus, Ohio, 43215

  • Grant Medical Center

    Columbus, Ohio, 43215

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • Mount Carmel Health Center West

    Columbus, Ohio, 43222

  • Doctors Hospital

    Columbus, Ohio, 43228

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Texas Oncology at Baylor Charles A Sammons Cancer Center

    Dallas, Texas, 75246

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle on Vermilion

    Danville, Illinois, 61832

  • Beaumont Hospital - Dearborn

    Dearborn, Michigan, 48124

  • Heartland Cancer Research NCORP

    Decatur, Illinois, 62526

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Delaware Radiation Oncology

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Ascension Saint John Hospital

    Detroit, Michigan, 48236

  • Hematology Oncology Associates of Central New York-East Syracuse

    East Syracuse, New York, 13057

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Green Bay Oncology - Escanaba

    Escanaba, Michigan, 49829

  • Willamette Valley Cancer Center

    Eugene, Oregon, 97401

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • UPMC Cancer Center at UPMC Horizon

    Farrell, Pennsylvania, 16121

  • Piedmont Fayette Hospital

    Fayetteville, Georgia, 30214

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Texas Oncology - Fort Worth Cancer Center

    Fort Worth, Texas, 76104

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Northeast Georgia Medical Center-Gainesville

    Gainesville, Georgia, 30501

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Adams Cancer Center

    Gettysburg, Pennsylvania, 17325

  • NorthShore University HealthSystem-Glenbrook Hospital

    Glenview, Illinois, 60026

  • Texas Oncology-Grapevine

    Grapevine, Texas, 76053

  • Green Bay Oncology at Saint Vincent Hospital

    Green Bay, Wisconsin, 54301-3526

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Green Bay Oncology Limited at Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

  • UPMC Cancer Centers - Arnold Palmer Pavilion

    Greensburg, Pennsylvania, 15601

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • Cherry Tree Cancer Center

    Hanover, Pennsylvania, 17331

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • AdventHealth Hendersonville

    Hendersonville, North Carolina, 28792

  • Hutchinson Area Health Care

    Hutchinson, Minnesota, 55350

  • Centerpoint Medical Center LLC

    Independence, Missouri, 64057

  • Green Bay Oncology - Iron Mountain

    Iron Mountain, Michigan, 49801

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

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

    Johnstown, Pennsylvania, 15901

  • Freeman Health System

    Joplin, Missouri, 64804

  • Mercy Hospital Joplin

    Joplin, Missouri, 64804

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Borgess Medical Center

    Kalamazoo, Michigan, 49048

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • North Kansas City Hospital

    Kansas City, Missouri, 64116

  • Heartland Hematology and Oncology Associates Incorporated

    Kansas City, Missouri, 64118

  • Research Medical Center

    Kansas City, Missouri, 64132

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • Lancaster Radiation Oncology

    Lancaster, Ohio, 43130

  • Lancaster General Hospital

    Lancaster, Pennsylvania, 17602

  • Sparrow Hospital

    Lansing, Michigan, 48912

  • Saint Luke's East - Lee's Summit

    Lee's Summit, Missouri, 64086

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Liberty Radiation Oncology Center

    Liberty, Missouri, 64068

  • Hematology Oncology Associates of Central New York-Liverpool

    Liverpool, New York, 13088

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Logan Regional Hospital

    Logan, Utah, 84321

  • Texas Oncology-Longview Cancer Center

    Longview, Texas, 75601

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

  • Los Angeles County-USC Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Holy Family Memorial Hospital

    Manitowoc, Wisconsin, 54221

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Saint John's Hospital - Healtheast

    Maplewood, Minnesota, 55109

  • Marietta Memorial Hospital

    Marietta, Ohio, 45750

  • Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • UPMC Cancer Center at UPMC McKeesport

    McKeesport, Pennsylvania, 15132

  • Summa Health Medina Medical Center

    Medina, Ohio, 44256

  • Froedtert Menomonee Falls Hospital

    Menomonee Falls, Wisconsin, 53051

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Health Partners Inc

    Minneapolis, Minnesota, 55454

  • Good Samaritan Regional Health Center

    Mount Vernon, Illinois, 62864

  • Knox Community Hospital

    Mount Vernon, Ohio, 43050

  • ProHealth D N Greenwald Center

    Mukwonago, Wisconsin, 53149

  • Intermountain Medical Center

    Murray, Utah, 84107

  • UPMC Cancer Center-Natrona Heights

    Natrona Heights, Pennsylvania, 15065

  • The Hospital of Central Connecticut

    New Britain, Connecticut, 06050

  • UPMC Jameson

    New Castle, Pennsylvania, 16105

  • Cancer Center of Western Wisconsin

    New Richmond, Wisconsin, 54017

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Licking Memorial Hospital

    Newark, Ohio, 43055

  • Newark Radiation Oncology

    Newark, Ohio, 43055

  • Carle Cancer Institute Normal

    Normal, Illinois, 61761

  • Eastern Connecticut Hematology and Oncology Associates

    Norwich, Connecticut, 06360

  • William Backus Hospital

    Norwich, Connecticut, 06360

  • Sutter Cancer Research Consortium

    Novato, California, 94945

  • ProHealth Oconomowoc Memorial Hospital

    Oconomowoc, Wisconsin, 53066

  • Saint Vincent Hospital Cancer Center at Oconto Falls

    Oconto Falls, Wisconsin, 54154

  • McKay-Dee Hospital Center

    Ogden, Utah, 84403

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Saint Joseph Hospital - Orange

    Orange, California, 92868

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Menorah Medical Center

    Overland Park, Kansas, 66209

  • Saint Luke's South Hospital

    Overland Park, Kansas, 66213

  • Paoli Memorial Hospital

    Paoli, Pennsylvania, 19301

  • Singing River Hospital

    Pascagoula, Mississippi, 39581

  • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center

    Pekin, Illinois, 61554

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • OSF Saint Francis Radiation Oncology at Peoria Cancer Center

    Peoria, Illinois, 61615

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61636

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Arizona Oncology-Deer Valley Center

    Phoenix, Arizona, 85027

  • UPMC-Presbyterian Hospital

    Pittsburgh, Pennsylvania, 15213

  • UPMC-Saint Margaret

    Pittsburgh, Pennsylvania, 15215

  • UPMC-Shadyside Hospital

    Pittsburgh, Pennsylvania, 15232

  • UPMC Jefferson Regional Radiation Oncology

    Pittsburgh, Pennsylvania, 15236

  • UPMC-Passavant Hospital

    Pittsburgh, Pennsylvania, 15237

  • UPMC-Saint Clair Hospital Cancer Center

    Pittsburgh, Pennsylvania, 15243

  • Saint Joseph Mercy Oakland

    Pontiac, Michigan, 48341

  • Lake Huron Medical Center

    Port Huron, Michigan, 48060

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Southern Ohio Medical Center

    Portsmouth, Ohio, 45662

  • Kansas City NCI Community Oncology Research Program

    Prairie Village, Kansas, 66208

  • Utah Valley Regional Medical Center

    Provo, Utah, 84604

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • University Hospitals Portage Medical Center

    Ravenna, Ohio, 44266

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Mercy Clinic-Rolla-Cancer and Hematology

    Rolla, Missouri, 65401

  • Hematology Oncology Associates of Central New York-Rome

    Rome, New York, 13440

  • Texas Oncology-Seton Williamson

    Round Rock, Texas, 78665

  • Texas Oncology - Round Rock Cancer Center

    Round Rock, Texas, 78681

  • William Beaumont Hospital-Royal Oak

    Royal Oak, Michigan, 48073

  • Rutherford Hospital

    Rutherfordton, North Carolina, 28139

  • Ascension Saint Mary's Hospital

    Saginaw, Michigan, 48601

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64506

  • Saint Joseph Oncology Inc

    Saint Joseph, Missouri, 64507

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Utah Cancer Specialists-Salt Lake City

    Salt Lake City, Utah, 84106

  • LDS Hospital

    Salt Lake City, Utah, 84143

  • California Pacific Medical Center-Pacific Campus

    San Francisco, California, 94115

  • Maine Medical Center- Scarborough Campus

    Scarborough, Maine, 04074

  • Arizona Oncology Services Foundation

    Scottsdale, Arizona, 85260

  • UPMC Cancer Center at UPMC Northwest

    Seneca, Pennsylvania, 16346

  • Saint Francis Regional Medical Center

    Shakopee, Minnesota, 55379

  • Spartanburg Medical Center

    Spartanburg, South Carolina, 29303

  • Cancer Care Northwest - Spokane South

    Spokane, Washington, 99202

  • Cancer Care Northwest-North Spokane

    Spokane, Washington, 99218

  • Cancer Research for the Ozarks NCORP

    Springfield, Missouri, 65804

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Springfield Regional Medical Center

    Springfield, Ohio, 45505

  • Saint Louis Cancer and Breast Institute-South City

    St Louis, Missouri, 63109

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Saint George Regional Medical Center

    St. George, Utah, 84770

  • Saint Vincent Hospital Cancer Center at Sturgeon Bay

    Sturgeon Bay, Wisconsin, 54235-1495

  • Green Bay Oncology - Sturgeon Bay

    Sturgeon Bay, Wisconsin, 54235

  • Texas Oncology Cancer Center Sugar Land

    Sugar Land, Texas, 77479

  • Hematology Oncology Associates of Central New York-Onondaga Hill

    Syracuse, New York, 13215

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • William Beaumont Hospital - Troy

    Troy, Michigan, 48085

  • Arizona Oncology Associates-West Orange Grove

    Tucson, Arizona, 85704

  • Natalie Warren Bryant Cancer Center at Saint Francis

    Tulsa, Oklahoma, 74136

  • Oklahoma Cancer Specialists and Research Institute-Tulsa

    Tulsa, Oklahoma, 74146

  • Warren Clinic Oncology-Tulsa

    Tulsa, Oklahoma, 74146

  • Tyler Cancer Center

    Tyler, Texas, 75702

  • UPMC Uniontown Hospital Radiation Oncology

    Uniontown, Pennsylvania, 15401

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • The Carle Foundation Hospital

    Urbana, Illinois, 61801

  • Sutter Solano Medical Center/Cancer Center

    Vallejo, California, 94589

  • PeaceHealth Southwest Medical Center

    Vancouver, Washington, 98664

  • Compass Oncology Vancouver

    Vancouver, Washington, 98684

  • Ridgeview Medical Center

    Waconia, Minnesota, 55387

  • Saint John Macomb-Oakland Hospital

    Warren, Michigan, 48093

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • UPMC Washington Hospital Radiation Oncology

    Washington, Pennsylvania, 15301

  • ProHealth Waukesha Memorial Hospital

    Waukesha, Wisconsin, 53188

  • Aspirus Regional Cancer Center

    Wausau, Wisconsin, 54401

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

  • Reading Hospital

    West Reading, Pennsylvania, 19611

  • Saint Ann's Hospital

    Westerville, Ohio, 43081

  • Rice Memorial Hospital

    Willmar, Minnesota, 56201

  • Southeast Clinical Oncology Research Consortium NCORP

    Winston-Salem, North Carolina, 27104

  • Minnesota Oncology Hematology PA-Woodbury

    Woodbury, Minnesota, 55125

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

  • Main Line Health NCORP

    Wynnewood, Pennsylvania, 19096

  • WellSpan Health-York Hospital

    York, Pennsylvania, 17403

  • Rush-Copley Healthcare Center

    Yorkville, Illinois, 60560

  • Genesis Healthcare System Cancer Care Center

    Zanesville, Ohio, 43701

Other trials in United States

Canada1 site

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

Other trials in Canada

About this study

Official title: Phase II Double-Blinded Placebo-Controlled Study of Bevacizumab With or Without AMG 386 in Patients With Recurrent Glioblastoma or Gliosarcoma

This partially randomized phase II trial with a safety run-in component studies the side effects and how well bevacizumab given with or without trebananib works in treating patients with brain tumors that have come back (recurrent). Immunotherapy with monoclonal antibodies, such as bevacizumab, may induce changes in the body's immune system and interfere with the ability of tumor cells to grow and spread. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving bevacizumab together with trebananib is more effective than bevacizumab alone in treating brain tumors.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety and tolerability of AMG 386 (trebananib) 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1). (closed to accrual 10/2/12) II. To assess the efficacy of AMG 386 in combination with bevacizumab 10 mg/kg every 2 weeks compared to bevacizumab monotherapy in bevacizumab-naive patients, as measured by 6-month progression-free survival (PFS6) (Cohort 2).

SECONDARY OBJECTIVES:

  1. To further assess the toxicity profile (Cohorts 1 and 2). II. To assess feasibility of AMG 386 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1 [closed to accrual 10/2/12]), as measured by the percentage of patients requiring dose reduction/interruption or discontinuation in the first 2 and subsequent cycles.

III. To determine the radiographic response rate (RR), median progression-free survival (PFS), and overall survival (OS) in bevacizumab-naive patients (Cohort 2).

IV. To assess the efficacy of AMG 386 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks in patients who have progressed while on bevacizumab, as measured by overall survival (OS) (cross-over from placebo arm of Cohort 2).

  1. To correlate outcome to treatment with tumor genotype, expression profile, and circulating angiogenesis biomarkers in tumor specimens (Cohort 2).

VI. To determine the RR, PFS6, and PFS in patients who have progressed while on bevacizumab therapy and receive AMG 386 in combination with bevacizumab (cross-over from placebo arm of Cohort 2).

VII. To determine the serum pharmacokinetics of AMG 386 in patients receiving bevacizumab (Cohort 1 and cross-over from placebo arm of Cohort 2).

OUTLINE: This is a safety study (cohort 1 [closed to accrual 10/2/12]) followed by a randomized study (cohort 2).

Cohort 1: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 and trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (closed to accrual 10/2/12)

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

ARM I: Patients receive bevacizumab and trebananib as in Cohort 1.

ARM II: Patients receive bevacizumab as in Arm I and placebo IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm I.

After completion of study treatment, patients are followed up at 30 days, every 2 months for 1 year, every 6 months for 1 year, and then annually thereafter.

Being tested
Bevacizumab, Laboratory Biomarker Analysis, Pharmacological Study, Placebo Administration, Trebananib
Medical subject headings
Glioblastoma, Gliosarcoma, Oligodendroglioma, Brain Neoplasms

What participants receive

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

  • BevacizumabBiological

    Also called ABP 215, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • Placebo AdministrationOther

    Given IV

  • TrebananibBiological

    Also called AMG 386, AMG386, Angiopoietin 1/2-Neutralizing Peptibody AMG 386

    Given IV

Study groups in NCT01609790
Study groupRoleWhat they receive
Arm I (bevacizumab and trebananib)ExperimentalPatients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Trebananib
Arm II (bevacizumab and placebo)Active comparatorPatients receive bevacizumab as in Arm I and placebo IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm I.
Receives: Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo Administration

What is being measured

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

  1. Number of Patients Experiencing of Dose-limiting Toxicity (Cohort 1)

    Dose-limiting toxicity (DLT), defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and meets any of the criteria below. Any DLT must be a toxicity possibly related to protocol treatment during first 4 weeks: grade 4 hematologic toxicity, grade 3/4 thrombocytopenia, or grade 3/4 non-hematologic toxicity; Gastrointestinal fistula, bowel perforation, intracranial hemorrhage, wound dehiscence, or reversible posterior leukoencephalopathy of any grade; Delay of treatment > 28 days. If 2+ of patients experience a DLT among 6 eligible patients, this drug combination will be considered unsafe and a lower dose of AMG will be explored; otherwise conclude that this drug combination is safe. The probability of claiming safe dose is no more than 16% when the true DLT rate is >45%, and the probability of claiming safe dose is at least 78% when the true DLT rate is <= 15%.

    Measured: From start of treatment to 4 weeks.

  2. Six-month Progression-free Survival (Cohort 2)

    As determined by central review of MRI exams, assessed using RANO criteria for progression that is defined by any of the following: > 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared to the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids; Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events; Any new lesion; Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose; Failure to return for evaluation due to death or deteriorating condition; Clear progression of non-measurable disease.

    Measured: From randomization to six months.

Secondary outcomes (5)

  1. Incidence of Grade 3+ Treatment-related Toxicity, Measured by CTCAE v. 4 (Cohort 2)

    Adverse events (AEs) are graded by using CTCAE 4.0. Possibly/probably/definitely related to protocol treatment AEs are considered.

    Measured: From start of treatment up to 3 years.

  2. Overall Survival (Cohort 2)

    Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 6 months.

    Measured: From randomization up to 3 years.

  3. Progression-free Survival (Cohort 2)

    Progression-free survival time is measured from randomization to the date of first progression or death or, otherwise, the last follow-up date on which the patient was reported alive. This analysis was planned to occur when all patients had been potentially followed for at least 6 months.

    Measured: From randomization up to 3 years.

  4. Radiographic Response Rate (Cohort 2)

    Proportion of patients with best overall response of complete response (CR) or partial response (PR) recorded from the start of the treatment until disease progression/recurrence. Response determined by site-reported radiology review of MRI exams using Response Assessment in Neuro-Oncology Criteria (RANO) criteria. CR: Complete disappearance of all enhancing measurable disease (MD) + non-measurable disease (NMD) sustained >= 4 wks; No new lesions; Stable or improved non-enhancing (T2/FLAIR) lesions; Off corticosteroids (or on physiologic replacement doses only); Stable/improved clinically. PR: >= 50% decrease vs. baseline of sum of products of perpendicular diameters of all measurable enhancing lesions sustained >= 4 wks; No progression of NMD; No new lesions; Stable/improved non-enhancing (T2/FLAIR) lesions on <= dose of corticosteroids vs. baseline scan; Corticosteroid dose at evaluation scan <= baseline scan dose; Stable or improved clinically. NMD only cannot be a CR or PR.

    Measured: From randomization up to 3 years.

  5. Percentage of Patients Requiring Dose Reduction/Interruption or Discontinuation in the First 2 and Subsequent Courses (Cohort 1)

    Feasibility of trebananib weekly in combination with bevacizumab every 2 weeks, measured by the percentage of patients requiring dose reduction/interruption or discontinuation in the first 2 and subsequent courses (Cohort 1)

    Measured: From randomization up to 3 years.

Timeline

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

  1. First posted1 Jun 2012 (estimated)
  2. Study start4 Jun 2012
  3. Primary completion2 Oct 2015
  4. Study completion20 May 2022

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
137 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01609790
Sponsor's protocol ID
NCI-2012-01969
Other IDs
NCI-2012-01969, S13-00759, CDR0000734205, RTOG-1122, RTOG-1122, RTOG-1122, U10CA180868, U10CA021661
Status last verified
May 2022
First submitted
30 May 2012
Last updated
21 Jul 2022
Data monitoring committee
No

Publications

  • Lee EQ, Zhang P, Wen PY, Gerstner ER, Reardon DA, Aldape KD, deGroot JF, Pan E, Raizer JJ, Kim LJ, Chmura SJ, Robins HI, Connelly JM, Battiste JD, Villano JL, Wagle N, Merrell RT, Wendland MM, Mehta MP. NRG/RTOG 1122: A phase 2, double-blinded, placebo-controlled study of bevacizumab with and without trebananib in patients with recurrent glioblastoma or gliosarcoma. Cancer. 2020 Jun 15;126(12):2821-2828. doi: 10.1002/cncr.32811. Epub 2020 Mar 10.

    PubMed 32154928

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Laboratory Biomarker Analysis and Pharmacological Study in people with Giant Cell Glioblastoma and Glioblastoma, run by National Cancer Institute (NCI) at 244 sites in 2 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 21 inclusion and 24 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 21 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 244 sites in United States, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 27 Feb 2017). 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?

Number of Patients Experiencing of Dose-limiting Toxicity (Cohort 1) (time frame: From start of treatment to 4 weeks.). 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 NCT01609790, 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 21 Jul 2022.

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