Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma
NCT ID: NCT01189266
Last Updated: 2021-10-28
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1/PHASE2
79 participants
INTERVENTIONAL
2010-08-09
2021-09-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
l. To estimate the maximum tolerated dose (MTD) or recommend a phase 2 dose of vorinostat given concurrently with radiation in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).
II. To define and describe the toxicities of vorinostat given concurrently with radiation in children with newly diagnosed DIPG.
III. To determine, in the context of this phase I/II trial, the anti-tumor activity of combining vorinostat with radiation, followed by maintenance vorinostat for twelve courses, in children with newly diagnosed DIPG, as measured by 12-month event-free survival (EFS) and overall survival (OS).
IV. To determine the toxicities of vorinostat for 12 additional courses after completion of vorinostat and radiation.
SECONDARY OBJECTIVES:
I. To measure non-homologous end-joining (NHEJ) activity in peripheral blood mononuclear cells (PBMCs) before treatment, at 2 weeks after starting vorinostat and radiation, and at the end of radiation.
II. To measure histone deacetylase 2 (HDAC2) levels and assess histone acetylation in PBMCs before treatment, at 2 weeks after starting vorinostat and radiation, and at the end of radiation.
III. To quantify deoxyribonucleic acid (DNA) repair proteins from the NHEJ and homologous recombination repair (HHR) pathways in tumors by either Western analysis or immunohistochemistry, if paraffin-embedded tumor is available.
OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.
Patients receive vorinostat orally (PO) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients undergo 3-dimensional (3D) conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. Patients then receive maintenance therapy comprising vorinostat PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm 1 Phase I Vorinostat 180 mg/m^2
Patients in phase I received vorinostat at 180 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
3-Dimensional Conformal Radiation Therapy
Undergo 3D conformal radiation therapy
Intensity-Modulated Radiation Therapy
Undergo intensity-modulated radiation therapy
Laboratory Biomarker Analysis
Correlative studies
Vorinostat
Given PO
Arm 2 Phase 1 Vorinostat 230 mg/m^2
Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
3-Dimensional Conformal Radiation Therapy
Undergo 3D conformal radiation therapy
Intensity-Modulated Radiation Therapy
Undergo intensity-modulated radiation therapy
Laboratory Biomarker Analysis
Correlative studies
Vorinostat
Given PO
Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
3-Dimensional Conformal Radiation Therapy
Undergo 3D conformal radiation therapy
Intensity-Modulated Radiation Therapy
Undergo intensity-modulated radiation therapy
Laboratory Biomarker Analysis
Correlative studies
Vorinostat
Given PO
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
3-Dimensional Conformal Radiation Therapy
Undergo 3D conformal radiation therapy
Intensity-Modulated Radiation Therapy
Undergo intensity-modulated radiation therapy
Laboratory Biomarker Analysis
Correlative studies
Vorinostat
Given PO
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must not have received any prior treatment except dexamethasone and/or surgery
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
* Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
* 0.8 mg/dL (3 to \< 6 years of age)
* 1 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)
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 110 U/L; for the purpose of this study, the ULN for SGPT (ALT) is 45 U/L
* Serum albumin \>= 2 g/dL
* Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants (with the exception of valproic acid) and seizures are well controlled
* Patients must be able to swallow capsules or liquids; patients dependent on nasogastric (NG) tube feeding are not permitted to receive protocol therapy
* Enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date
Exclusion Criteria
* Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible
* Patients must not currently be receiving enzyme inducing anticonvulsants
* Patients on valproic acid must discontinue valproic acid for at least 2 weeks before starting protocol therapy
* Patients receiving coumadin, heparin, low-molecular weight heparin, or any other anti-coagulants are not eligible for study entry
* Patients receiving acetylsalicylic acid (ASA) (\> 81 mg/day), non-steroidal anti-inflammatory drugs, clopidogrel (Plavix), dipyridamole (Persantine), or any other drug that inhibits platelet function are not eligible for study entry
* Patients who have an uncontrolled infection are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
37 Months
21 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Jack M Su
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Children's Hospital of Alabama
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Providence Hospital
Mobile, Alabama, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Highlands Oncology Group
Rogers, Arkansas, United States
Kaiser Permanente-Deer Valley Medical Center
Antioch, California, United States
Kaiser Permanente Downey Medical Center
Downey, California, United States
Kaiser Permanente-Fremont
Fremont, California, United States
Kaiser Permanente-Fresno
Fresno, California, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
Cedars Sinai Medical Center
Los Angeles, California, United States
Valley Children's Hospital
Madera, California, United States
Contra Costa Regional Medical Center
Martinez, California, United States
El Camino Hospital
Mountain View, California, United States
Highland General Hospital
Oakland, California, United States
Alta Bates Summit Medical Center - Summit Campus
Oakland, California, United States
Bay Area Tumor Institute
Oakland, California, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States
Kaiser Permanente-Oakland
Oakland, California, United States
Children's Hospital of Orange County
Orange, California, United States
Kaiser Permanente-Redwood City
Redwood City, California, United States
Kaiser Permanente-Richmond
Richmond, California, United States
Kaiser Permanente-Roseville
Roseville, California, United States
Kaiser Permanente-South Sacramento
Sacramento, California, United States
Kaiser Permanente - Sacramento
Sacramento, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
Kaiser Permanente-San Francisco
San Francisco, California, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California, United States
Kaiser Permanente San Leandro
San Leandro, California, United States
Doctors Medical Center- JC Robinson Regional Cancer Center
San Pablo, California, United States
Kaiser Permanente-San Rafael
San Rafael, California, United States
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, United States
Kaiser Permanente-Santa Rosa
Santa Rosa, California, United States
Kaiser Permanente-South San Francisco
South San Francisco, California, United States
Kaiser Permanente-Stockton
Stockton, California, United States
Kaiser Permanente Medical Center-Vacaville
Vacaville, California, United States
Kaiser Permanente-Vallejo
Vallejo, California, United States
Kaiser Permanente-Walnut Creek
Walnut Creek, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Lee Memorial Health System
Fort Myers, Florida, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
AdventHealth Orlando
Orlando, Florida, United States
Arnold Palmer Hospital for Children
Orlando, Florida, United States
Nemours Children's Clinic - Orlando
Orlando, Florida, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
Nemours Children's Hospital
Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Memorial Health University Medical Center
Savannah, Georgia, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, United States
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, United States
Saint Anthony's Health
Alton, Illinois, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Decatur Memorial Hospital
Decatur, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
Good Samaritan Regional Health Center
Mount Vernon, Illinois, United States
Edward Hospital/Cancer Center
Naperville, Illinois, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, United States
Memorial Medical Center
Springfield, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Blank Children's Hospital
Des Moines, Iowa, United States
Baptist Health Lexington
Lexington, Kentucky, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Norton Children's Hospital
Louisville, Kentucky, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Michigan Cancer Research Consortium NCORP
Ann Arbor, Michigan, United States
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Beaumont Hospital - Dearborn
Dearborn, Michigan, United States
Ascension Saint John Hospital
Detroit, Michigan, United States
Hurley Medical Center
Flint, Michigan, United States
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States
Allegiance Health
Jackson, Michigan, United States
Sparrow Hospital
Lansing, Michigan, United States
Saint Mary Mercy Hospital
Livonia, Michigan, United States
Saint Joseph Mercy Oakland
Pontiac, Michigan, United States
Lake Huron Medical Center
Port Huron, Michigan, United States
Ascension Saint Mary's Hospital
Saginaw, Michigan, United States
Saint John Macomb-Oakland Hospital
Warren, Michigan, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Singing River Hospital
Pascagoula, Mississippi, United States
Saint Francis Medical Center
Cape Girardeau, Missouri, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Cancer Research for the Ozarks NCORP
Springfield, Missouri, United States
Mercy Hospital Springfield
Springfield, Missouri, United States
CoxHealth South Hospital
Springfield, Missouri, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
St Louis, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Saint Louis-Cape Girardeau CCOP
St Louis, Missouri, United States
Billings Clinic Cancer Center
Billings, Montana, United States
Saint Vincent Healthcare
Billings, Montana, United States
Montana Cancer Consortium NCORP
Billings, Montana, United States
Saint Vincent Frontier Cancer Center
Billings, Montana, United States
Bozeman Deaconess Hospital
Bozeman, Montana, United States
Benefis Healthcare- Sletten Cancer Institute
Great Falls, Montana, United States
Great Falls Clinic
Great Falls, Montana, United States
Saint Peter's Community Hospital
Helena, Montana, United States
Glacier Oncology PLLC
Kalispell, Montana, United States
Kalispell Regional Medical Center
Kalispell, Montana, United States
Saint Patrick Hospital - Community Hospital
Missoula, Montana, United States
CHI Health Good Samaritan
Kearney, Nebraska, United States
Morristown Medical Center
Morristown, New Jersey, United States
Saint Peter's University Hospital
New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
Newark, New Jersey, United States
Overlook Hospital
Summit, New Jersey, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
Mission Hospital
Asheville, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Wayne Memorial Hospital
Goldsboro, North Carolina, United States
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, United States
Iredell Memorial Hospital
Statesville, North Carolina, United States
Southeast Clinical Oncology Research Consortium NCORP
Winston-Salem, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Cleveland Clinic Akron General
Akron, Ohio, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Saint Charles Health System
Bend, Oregon, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, United States
Oregon Health and Science University
Portland, Oregon, United States
Penn State Children's Hospital
Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
AnMed Health Hospital
Anderson, South Carolina, United States
Prisma Health Richland Hospital
Columbia, South Carolina, United States
Saint Francis Hospital
Greenville, South Carolina, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
Greenville Cancer Treatment Center
Greenville, South Carolina, United States
Carolina Blood and Cancer Care Associates PA-Lancaster
Lancaster, South Carolina, United States
Spartanburg Medical Center
Spartanburg, South Carolina, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Driscoll Children's Hospital
Corpus Christi, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
Cancer Care Center at Island Hospital
Anacortes, Washington, United States
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, United States
Harrison HealthPartners Hematology and Oncology-Bremerton
Bremerton, Washington, United States
Highline Medical Center-Main Campus
Burien, Washington, United States
Kadlec Clinic Hematology and Oncology
Kennewick, Washington, United States
Skagit Valley Hospital
Mount Vernon, Washington, United States
Harrison HealthPartners Hematology and Oncology-Poulsbo
Poulsbo, Washington, United States
Harborview Medical Center
Seattle, Washington, United States
Minor and James Medical PLLC
Seattle, Washington, United States
Seattle Children's Hospital
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Kaiser Permanente Washington
Seattle, Washington, United States
Swedish Medical Center-First Hill
Seattle, Washington, United States
University of Washington Medical Center - Montlake
Seattle, Washington, United States
PeaceHealth United General Medical Center
Sedro-Woolley, Washington, United States
Cancer Care Northwest - Spokane South
Spokane, Washington, United States
Evergreen Hematology and Oncology PS
Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States
Wenatchee Valley Hospital and Clinics
Wenatchee, Washington, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
Yakima, Washington, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Welch Cancer Center
Sheridan, Wyoming, United States
Royal Children's Hospital-Brisbane
Herston, Queensland, Australia
Queensland Children's Hospital
South Brisbane, Queensland, Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
Hospital for Sick Children
Toronto, Ontario, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Countries
Review the countries where the study has at least one active or historical site.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2011-02600
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACNS0927
Identifier Type: -
Identifier Source: secondary_id
S12-02793
Identifier Type: -
Identifier Source: secondary_id
COG-ACNS0927
Identifier Type: -
Identifier Source: secondary_id
CDR0000683459
Identifier Type: -
Identifier Source: secondary_id
ACNS0927
Identifier Type: OTHER
Identifier Source: secondary_id
ACNS0927
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2011-02600
Identifier Type: -
Identifier Source: org_study_id