Brain Stem GliomaPhase 2/3NCT01236560

Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma

A Phase 2/3 study testing Bevacizumab, Temozolomide and Vorinostat in people with Brain Stem Glioma and Cerebral Astrocytoma, run by National Cancer Institute (NCI) at 132 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

Who is it for?: Ages 3 to 21 years
Conditions the study is for: Brain Stem Glioma, Cerebral Astrocytoma, Childhood Cerebellar Anaplastic Astrocytoma
What is being tested?: Bevacizumab, Temozolomide and Vorinostat
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 101 participants
Where: 132 sitesin 2 countries
Study dates: 26 Jan 2011to 31 Dec 2023
Phase: Phase 2/3
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 3 to 21 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Newly diagnosed high-grade glioma
Anaplastic astrocytoma
Glioblastomamultiforme
Gliosarcoma
Primary spinal cord malignant glioma allowed
No oligodendroglioma oroligoastrocytoma

Show all 56Show fewer

Patient must have histological verification of diagnosis
No M+ disease (defined as evidence of neuraxis dissemination)
No positive CSF cytology
ECOG performance status (PS) 0-2
Karnofsky PS 50-100% (patients > 16 years of age)
Lansky PS 50-100% (patients ≤ 16 years of age)
ANC ≥ 1,000/μL
Platelet count ≥ 100,000/μL
Hemoglobin ≥ 8.0 mg/dL (transfusion independent)
Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:
0.4 mg/dL (1 month to < 6 months of age)
0.5 mg/dL (6 months to < 1 year of age)
0.6 mg/dL (1 to < 2 years of age)
0.8 mg/dL (2 to < 6 years of age)
1.0 mg/dL (6 to < 10 years of age)
1.2 mg/dL (10 to < 13 years of age)
1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
Proteinuria < 2+ OR urine; protein ratio (UPC) ≤ 0.5
If UPC > 0.5, a 24-hour urine protein should be obtained and level should be < 1,000 mg of protein
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT < 2.5 times ULN
Serum albumin ≥ 2 g/dL
PT INR ≤ 1.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during all study therapy and for ≥ 6 months after completion of bevacizumab
Hypertension well controlled (≤ 95^th percentile for age and height if patient is ≤ 17years) by stable doses of medication allowed
For patients > 17 years, systolic blood pressure (BP) ≤ 150 mm Hg or diastolic BP ≤ 100 mm Hg)
Seizure disorder allowed provided patient is well-controlled and on nonenzyme-inducing anticonvulsants
No history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, ≥ grade 2 heart failure, or serious and inadequately controlled cardiac arrhythmia
No known bleeding diathesis or coagulopathy
No prior arterial thromboembolic events, including transient ischemic attacks orcerebrovascular accidents
No prior diagnosis of a deep venous thrombosis, including pulmonary embolism, and no known thrombophilic condition (e.g., protein S, protein C, antithrombin III deficiency, Factor V Leiden or Factor II G202'0A mutation, homocysteinemia, or antiphospholipid antibody syndrome)
No history of an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
No serious or non-healing wound, ulcer, or bone fracture
No evidence of significant postoperative intracranial hemorrhage, defined as > 1 cm of blood on postoperative MRI scan (potentially in addition to the postoperative scan) obtained within the past 14days
No history of allergic reaction to Chinese hamster ovary cell products or other recombinanthuman antibodies
No more than 31 days since definitive surgery
Must not have received any prior chemotherapy, radiotherapy, immunotherapy, or bone marrow transplant
More than 7 days since major surgical procedure and recovered
For patients scheduled to receive bevacizumab:
More than 28 days since major procedure
More than 14 days since intermediate procedure
More than 7 days since minor procedure (lumbar picture or placement of PICC lines are not considered minor procedures)
No other current anti-cancer agents
No concurrent nonsteroidal anti-inflammatory medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase activity
No concurrent enzyme inducing anticonvulsants
No concurrent HDAC inhibitors (e.g., valproic acid)
No concurrent anticoagulants including systemic thrombolytic agents, heparin, low molecular weight heparins, or warfarin except as required to maintain patency of pre-existing permanent vascular catheters or for prevention of thrombosis in the post-operative period

Who cannot join

None listed.

Trial locations and contacts

132 sites in 2 countries.

Country

City, postcode or hospital

132 sites in 2 countries

United States124 sites

Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Albany Medical Center
Albany, New York, 12208
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
Children's Hospital of Alabama
Birmingham, Alabama, 35233
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Tufts Children's Hospital
Boston, Massachusetts, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
West Virginia University Charleston Division
Charleston, West Virginia, 25304
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Dayton Children's Hospital
Dayton, Ohio, 45404
Blank Children's Hospital
Des Moines, Iowa, 50309
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Kaiser Permanente Downey Medical Center
Downey, California, 90242
Michigan State University Clinical Center
East Lansing, Michigan, 48824
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234
Cook Children's Medical Center
Fort Worth, Texas, 76104
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, 49503
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Greenville Cancer Treatment Center
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
Nevada Cancer Research Foundation NCORP
Las Vegas, Nevada, 89169
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Loma Linda University Medical Center
Loma Linda, California, 92354
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Cedars Sinai Medical Center
Los Angeles, California, 90048
Mattel Children's Hospital UCLA
Los Angeles, California, 90095
Norton Children's Hospital
Louisville, Kentucky, 40202
Valley Children's Hospital
Madera, California, 93636
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Nicklaus Children's Hospital
Miami, Florida, 33155
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Morristown Medical Center
Morristown, New Jersey, 07960
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Yale University
New Haven, Connecticut, 06520
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
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
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Orange County
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Oncology Group
Philadelphia, Pennsylvania, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Oregon Health and Science University
Portland, Oregon, 97239
Naval Medical Center - Portsmouth
Portsmouth, Virginia, 23708-2197
Rhode Island Hospital
Providence, Rhode Island, 02903
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
Primary Children's Hospital
Salt Lake City, Utah, 84113
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
UCSF Medical Center-Parnassus
San Francisco, California, 94143
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Memorial Health University Medical Center
Savannah, Georgia, 31404
Seattle Children's Hospital
Seattle, Washington, 98105
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Overlook Hospital
Summit, New Jersey, 07902
State University of New York Upstate Medical University
Syracuse, New York, 13210
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Scott and White Memorial Hospital
Temple, Texas, 76508
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157

Other trials in United States

Canada8 sites

IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: A Randomized Phase II/III Study of Vorinostat and Local Irradiation OR Temozolomide and Local Irradiation OR Bevacizumab and Local Irradiation Followed by Maintenance Bevacizumab and Temozolomide in Children With Newly Diagnosed High-Grade Gliomas

This randomized phase II/III trial is studying vorinostat, temozolomide, or bevacizumab to see how well they work compared with each other when given together with radiation therapy followed by bevacizumab and temozolomide in treating young patients with newly diagnosed high-grade glioma. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving vorinostat is more effective then temozolomide or bevacizumab when given together with radiation therapy in treating glioma.

Read the detailed description

PRIMARY OBJECTIVES:

To identify the dose of vorinostat that is feasible when given in combination with radiotherapy (RT) in patients with newly diagnosed high-grade gliomas (HGG). II. To compare 1-year event-free survival of patients with newly diagnosed HGG treated with vorinostat (using MTD) versus bevacizumab versus temozolomide when given in combination with RT followed by maintenance therapy with bevacizumab and temozolomide. (Phase II) III. To compare the event-free survival of patients with newly diagnosed HGG treated with the superior chemoradiotherapy (from phase II portion) versus temozolomide given in combination with RT followed by maintenance chemotherapy with bevacizumab and temozolomide. (Phase III)

SECONDARY OBJECTIVES:

To evaluate the anti-tumor activity, as measured by event-free survival (EFS), progression-free survival (PFS), and overall survival (OS), of patients with newly diagnosed HGG treated with vorinostat, bevacizumab, or temozolomide when given in combination with RT followed by maintenance chemotherapy with bevacizumab and temozolomide. II. To define and evaluate the toxicities of each of the treatment arms of the study.

III. To conduct gene expression profiling and SNP arrays in patients with newly diagnosed HGG.

IV. To assess telomerase activity, hTert expression, and telomere length in patients with newly diagnosed HGG. V. To document changes in perfusion and diffusion using MR imaging at baseline, prior to, during (prior to course 3), and after maintenance therapy with bevacizumab and temozolomide.

VI. To correlate functional changes in tumor with responses to bevacizumab treatment using MR diffusion/perfusion imaging. VII. To correlate the results of the bevacizumab biology studies in serum or tumor with EFS.

VIII. To explore the prognostic significance of MGMT status for patients newly diagnosed with HGG treated with combined surgery, radiation, chemotherapy, and anti-angiogenic therapy.

OUTLINE: This is a multicenter, feasibility, dose-escalation study of vorinostat, followed by a phase II study, followed by a phase III study.

FEASIBILITY STUDY: Patients undergo 3-D conformal radiotherapy (RT) or intensity-modulated RT 5 days a week for 6 weeks. Patients also receive vorinostat orally (PO) once daily on days 1-5. Courses repeat every week for 6 weeks in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and temozolomide PO on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

PHASE II STUDY: Patients are stratified according to extent of resection (near total resection or gross total resection vs other) and histology (glioblastoma multiforme vs other). Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients undergo RT 5 days a week for 6 weeks and receive vorinostat at the maximum-tolerated dose determined in the feasibility study.

ARM II: Patients undergo RT as in the feasibility arm and receive temozolomide PO once daily for 42 days by day 5 of RT.

ARM III: Patients undergo RT as in the feasibility arm and receive bevacizumab IV over 30-90 minutes on days 22 and 36.

Maintenance therapy in arms I, II, III: Patients in all arms receive maintenance therapy as in the feasibility study.

PHASE III study: Patients are randomized to 1 of 2 treatment arms.

ARM IV: Patients receive RT and temozolomide as in phase II, arm II.

ARM V: Patients receive treatment as in phase II, arm I or phase II, arm III, whichever was established as the superior chemoradiotherapy arm in phase II.

Maintenance Therapy: Beginning 4 weeks after completion of chemoradiotherapy, patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and temozolomide PO on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Some patients undergo blood and tumor tissue sample (from surgery) collection for telomerase activity, hTert expression, telomere length, and gene expression profiling and SNP arrays analysis.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

Conditions: Brain Stem Glioma, Cerebral Astrocytoma, Childhood Cerebellar Anaplastic Astrocytoma, Childhood Cerebral Anaplastic Astrocytoma, Childhood Spinal Cord Neoplasm
Being tested: Bevacizumab, Temozolomide, Vorinostat
Medical subject headings: Astrocytoma, Spinal Cord 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
TemozolomideDrug
Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831
Given PO
VorinostatDrug
Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid
Given PO

Study groups in NCT01236560
Study group	Role	What they receive
Arm I (vorinostat, Phase II Arm A)	Experimental	Patients undergo RT 5 days a week for 6 weeks and receive vorinostat at the maximum-tolerated dose determined in the feasibility study. Patients receive Maintenance therapy of bevacizumab 10mg/kg/dose every 2 weeks and temozolomide 200 mg/m2/dose Days 1-5, for up to twelve cycles in the absence of progressive disease and unacceptable toxicities. Receives: Biological: Bevacizumab; Drug: Temozolomide; Drug: Vorinostat
Arm II (temozolomide, Phase II Arm B)	Experimental	Patients undergo RT as in the feasibility arm and receive temozolomide PO once daily for 42 days by day 5 of RT. Patients receive Maintenance therapy of bevacizumab 10mg/kg/dose every 2 weeks and temozolomide 200 mg/m2/dose Days 1-5, for up to twelve cycles in the absence of progressive disease and unacceptable toxicities. Receives: Biological: Bevacizumab; Drug: Temozolomide
Arm III (Bevacizumab, Phase II Arm)	Experimental	Patients undergo RT as in the feasibility arm and receive bevacizumab IV over 30-90 minutes on days 22 and 36. Patients receive Maintenance therapy of bevacizumab 10mg/kg/dose every 2 weeks and temozolomide 200 mg/m2/dose Days 1-5, for up to twelve cycles in the absence of progressive disease and unacceptable toxicities. Receives: Biological: Bevacizumab; Drug: Temozolomide
Arm IV (temozolomide, Phase 3 Arm B)	Experimental	Patients undergo RT as in the Arm II and receive temozolomide PO once daily for 42 days beginning on day 5 of RT. Patients receive Maintenance therapy of bevacizumab 10mg/kg/dose every 2 weeks and temozolomide 200 mg/m2/dose Days 1-5, for up to twelve cycles in the absence of progressive disease and unacceptable toxicities. Receives: Biological: Bevacizumab; Drug: Temozolomide
Arm V (vorinostat/bevacizumab, Phase 3, Chemoradiotherapy)	Experimental	Patients receive treatment as in phase II, arm I or phase II, arm III, whichever was established as superior in phase II. Patients receive Maintenance therapy of bevacizumab 10mg/kg/dose every 2 weeks and temozolomide 200 mg/m2/dose Days 1-5, for up to twelve cycles in the absence of progressive disease and unacceptable toxicities. Receives: Biological: Bevacizumab; Drug: Temozolomide; Drug: Vorinostat
Feasibility (vorinostat)	Experimental	Patients undergo RT 5 days a week for 6 weeks and receive vorinostat at 230 mg/m2/day. In the event of 2 or more DLTs, participants will de-escalate to vorinostat at 180 mg/m2/day. Patients receive Maintenance therapy of bevacizumab 10mg/kg/dose every 2 weeks and temozolomide 200 mg/m2/dose Days 1-5, for up to twelve cycles in the absence of progressive disease and unacceptable toxicities. Receives: Biological: Bevacizumab; Drug: Temozolomide; Drug: Vorinostat

What is being measured

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

Maximum Tolerated Dose (MTD) of Vorinostat
The dose of vorinostat in mg/sq m/day to be administered with combination chemotherapy and radiation therapy.
Measured: 10 weeks
Event-free Survival
Time from enrollment to disease progression, diagnosis of a second malignant neoplasm, death or last follow-up, whichever occurs first. Disease progression is evaluated according to the COG criteria for measurement of brain tumors and is defined to be a ≥ 25% increase in the product of perpendicular diameters of ANY target lesion, taking as reference the smallest product observed since the start of treatment; OR the appearance of one or more new lesions, OR worsening neurologic status not explained by causes unrelated to tumor progression (e.g., anticonvulsant or corticosteroid toxicity, electrolyte disturbances, sepsis, hyperglycemia, presumed post-therapy swelling etc) PLUS any increase in tumor cross-sectional area (or tumor volume).
Measured: 1 year after enrollment

Secondary outcomes (2)

Overall Survival
Time from enrollment to death or last follow-up, whichever occurs first.
Measured: 1 year after enrollment
Cumulative Incidence of Disease Progression in Each Treatment Arm
Cumulative incidence of progression where death from any cause prior to progression and diagnosis of a second malignant neoplasm prior to progression are considered competing events. Disease progression is evaluated according to the COG criteria for measurement of brain tumors and is defined to be a ≥ 25% increase in the product of perpendicular diameters of ANY target lesion, taking as reference the smallest product observed since the start of treatment; OR the appearance of one or more new lesions, OR worsening neurologic status not explained by causes unrelated to tumor progression (e.g., anticonvulsant or corticosteroid toxicity, electrolyte disturbances, sepsis, hyperglycemia, presumed post-therapy swelling etc) PLUS any increase in tumor cross-sectional area (or tumor volume).
Measured: 1 year after enrollment

Timeline

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

26 Jan 201131 Dec 2023

First posted8 Nov 2010 (estimated)
Study start26 Jan 2011
Primary completion30 Jun 2023
Study completion31 Dec 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Brain Stem GliomaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 101 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01236560
Sponsor's protocol ID: NCI-2011-02616
Other IDs: NCI-2011-02616, CDR0000688443, ACNS0822, 11-00910, ACNS0822, ACNS0822, U10CA180886, U10CA098543
Status last verified: Jan 2024
First submitted: 5 Nov 2010
Last updated: 20 Feb 2024
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy
Neuroblastoma, Diffuse Intrinsic Pontine Glioma
Active, not recruitingPhase 2
Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
Glioblastoma, Medulloblastoma
Not yet recruitingPhase 1
IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Newly Diagnosed and Recurrent Pediatric High-grade Glioma (pHGG) and Newly Diagnosed Diffuse Intrinsic Pontine Glioma (ndDIPG)
High-grade Glioma, Diffuse Intrinsic Pontine Glioma
RecruitingPhase 2
A Study of VRT106 in Combination With Radiotherapy in Adult Patients With Diffuse Midline Glioma / Diffuse Intrinsic Pontine Glioma
Diffuse Midline Glioma, H3 K27M-Mutant, Diffuse Intrinsic Pontine Glioma
Not yet recruitingPhase 1
Immune Modulatory DC Vaccine Against Brain Tumor
Diffuse Intrinsic Pontine Glioma or Glioblastoma

All Brain Stem Glioma trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Phase II/III Study of Vorinostat and Local Irradiation OR Temozolomide and Local Irradiation OR Bevacizumab and Local Irradiation Followed by Maintenance Bevacizumab and Temozolomide in Children With Newly Diagnosed High-Grade Gliomas
ClinicalTrials.gov ID: NCT01236560
Acronym / sponsor ID: NCI-2011-02616
Conditions: Brain Stem Glioma, Cerebral Astrocytoma, Childhood Cerebellar Anaplastic Astrocytoma, Childhood Cerebral Anaplastic Astrocytoma, Childhood Spinal Cord Neoplasm
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 101 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 26 Jan 2011 (actual)
Primary completion: 30 Jun 2023 (actual)
Study completion: 31 Dec 2023 (actual)
First posted: 8 Nov 2010 (estimated)
Results: Posted 22 Jun 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

To identify the dose of vorinostat that is feasible when given in combination with radiotherapy (RT) in patients with newly diagnosed high-grade gliomas (HGG). II. To compare 1-year event-free survival of patients with newly diagnosed HGG treated with vorinostat (using MTD) versus bevacizumab versus temozolomide when given in combination with RT followed by maintenance therapy with bevacizumab and temozolomide. (Phase II) III. To compare the event-free survival of patients with newly diagnosed HGG treated with the superior chemoradiotherapy (from phase II portion) versus temozolomide given in combination with RT followed by maintenance chemotherapy with bevacizumab and temozolomide. (Phase III)

SECONDARY OBJECTIVES:

To evaluate the anti-tumor activity, as measured by event-free survival (EFS), progression-free survival (PFS), and overall survival (OS), of patients with newly diagnosed HGG treated with vorinostat, bevacizumab, or temozolomide when given in combination with RT followed by maintenance chemotherapy with bevacizumab and temozolomide. II. To define and evaluate the toxicities of each of the treatment arms of the study.