Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma
A Phase 1/2 Study of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) and Local Irradiation, Followed by Maintenance SAHA in Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas (DIPG)
8 other identifiers
interventional
79
3 countries
180
Brief Summary
This phase I/II trial studies the side effects and best dose of vorinostat and to see how well it works when given together with radiation therapy followed by maintenance therapy with vorinostat in treating younger patients with newly diagnosed diffuse intrinsic pontine glioma (a brainstem tumor). Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vorinostat together with radiation therapy may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2010
Longer than P75 for phase_1
180 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 9, 2010
CompletedFirst Submitted
Initial submission to the registry
August 25, 2010
CompletedFirst Posted
Study publicly available on registry
August 26, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2017
CompletedResults Posted
Study results publicly available
March 3, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2021
CompletedOctober 28, 2021
October 1, 2021
6.9 years
August 25, 2010
July 5, 2019
October 5, 2021
Conditions
Outcome Measures
Primary Outcomes (4)
Maximum Tolerated Dose (MTD) of Vorinostat
The dose of vorinostat in mg/sqm/day to be administered with combination chemotherapy and radiation therapy
Planned 7 weeks during chemoradiotherapy
Event-Free Survival
Time from enrollment to disease progression, diagnosis of a second malignant neoplasm, death or last follow-up, whichever occurs first.
2 years after study enrollment
Incidence of Toxicity During Chemoradiation Therapy
Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
Planned 7 weeks during chemoradiotherapy
Incidence of Toxicity During Maintenance Therapy
Proportion of patients who experience any grade 3 or higher CTC AE Version 4 adverse experience
Planned 12 months of maintenance with Vorinostat
Secondary Outcomes (4)
Overall Survival
2 years after study enrollment
Change in H3 and H4 Acetylation Levels in PBMCs
Baseline to up to 7 weeks
Change in NHEJ Activity in PBMCs
Baseline to up to 7 weeks
Levels of DNA Repair Proteins in Paraffin-embedded Blocks, Measured Via Immunohistochemistry or Western Analysis
Baseline
Study Arms (3)
Arm 1 Phase I Vorinostat 180 mg/m^2
EXPERIMENTALPatients 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.
Arm 2 Phase 1 Vorinostat 230 mg/m^2
EXPERIMENTALPatients 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.
Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2
EXPERIMENTALPatients 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.
Interventions
Undergo 3D conformal radiation therapy
Undergo intensity-modulated radiation therapy
Correlative studies
Given PO
Eligibility Criteria
You may qualify if:
- Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons, are eligible without histologic confirmation; patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or anaplastic mixed glioma; patients with juvenile pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible; patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician
- 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:
- mg/dL (3 to \< 6 years of age)
- mg/dL (6 to \< 10 years of age)
- mg/dL (10 to \< 13 years of age)
- mg/dL (male) or 1.4 mg/dL (female) (13 to \< 16 years of age)
- 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
- +3 more criteria
You may not qualify if:
- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (180)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
Providence Hospital
Mobile, Alabama, 36608, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
Highlands Oncology Group
Rogers, Arkansas, 72758, United States
Kaiser Permanente-Deer Valley Medical Center
Antioch, California, 94531, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
Kaiser Permanente-Fremont
Fremont, California, 94538, United States
Kaiser Permanente-Fresno
Fresno, California, 93720, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Valley Children's Hospital
Madera, California, 93636, United States
Contra Costa Regional Medical Center
Martinez, California, 94553-3156, United States
El Camino Hospital
Mountain View, California, 94040, United States
Highland General Hospital
Oakland, California, 94602, United States
Alta Bates Summit Medical Center - Summit Campus
Oakland, California, 94609, United States
Bay Area Tumor Institute
Oakland, California, 94609, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Kaiser Permanente-Redwood City
Redwood City, California, 94063, United States
Kaiser Permanente-Richmond
Richmond, California, 94801, United States
Kaiser Permanente-Roseville
Roseville, California, 95661, United States
Kaiser Permanente-South Sacramento
Sacramento, California, 95823, United States
Kaiser Permanente - Sacramento
Sacramento, California, 95825, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
Kaiser Permanente-San Francisco
San Francisco, California, 94115, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California, 95119, United States
Kaiser Permanente San Leandro
San Leandro, California, 94577, United States
Doctors Medical Center- JC Robinson Regional Cancer Center
San Pablo, California, 94806, United States
Kaiser Permanente-San Rafael
San Rafael, California, 94903, United States
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, 95051, United States
Kaiser Permanente-Santa Rosa
Santa Rosa, California, 95403, United States
Kaiser Permanente-South San Francisco
South San Francisco, California, 94080, United States
Kaiser Permanente-Stockton
Stockton, California, 95210, United States
Kaiser Permanente Medical Center-Vacaville
Vacaville, California, 95688, United States
Kaiser Permanente-Vallejo
Vallejo, California, 94589, United States
Kaiser Permanente-Walnut Creek
Walnut Creek, California, 94596, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Lee Memorial Health System
Fort Myers, Florida, 33901, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
AdventHealth Orlando
Orlando, Florida, 32803, United States
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806, United States
Orlando Health Cancer Institute
Orlando, Florida, 32806, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Memorial Health University Medical Center
Savannah, Georgia, 31404, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813, United States
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, 96819, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706, United States
Saint Anthony's Health
Alton, Illinois, 62002, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Good Samaritan Regional Health Center
Mount Vernon, Illinois, 62864, United States
Edward Hospital/Cancer Center
Naperville, Illinois, 60540, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637, United States
Memorial Medical Center
Springfield, Illinois, 62781, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Blank Children's Hospital
Des Moines, Iowa, 50309, United States
Baptist Health Lexington
Lexington, Kentucky, 40503, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Michigan Cancer Research Consortium NCORP
Ann Arbor, Michigan, 48106, United States
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, 48106, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Beaumont Hospital - Dearborn
Dearborn, Michigan, 48124, United States
Ascension Saint John Hospital
Detroit, Michigan, 48236, United States
Hurley Medical Center
Flint, Michigan, 48503, United States
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, 48532, United States
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, 49503, United States
Allegiance Health
Jackson, Michigan, 49201, United States
Sparrow Hospital
Lansing, Michigan, 48912, United States
Saint Mary Mercy Hospital
Livonia, Michigan, 48154, United States
Saint Joseph Mercy Oakland
Pontiac, Michigan, 48341, United States
Lake Huron Medical Center
Port Huron, Michigan, 48060, United States
Ascension Saint Mary's Hospital
Saginaw, Michigan, 48601, United States
Saint John Macomb-Oakland Hospital
Warren, Michigan, 48093, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Singing River Hospital
Pascagoula, Mississippi, 39581, United States
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cancer Research for the Ozarks NCORP
Springfield, Missouri, 65804, United States
Mercy Hospital Springfield
Springfield, Missouri, 65804, United States
CoxHealth South Hospital
Springfield, Missouri, 65807, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Saint Louis Cancer and Breast Institute-South City
St Louis, Missouri, 63109, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Saint Louis-Cape Girardeau CCOP
St Louis, Missouri, 63141, United States
Billings Clinic Cancer Center
Billings, Montana, 59101, United States
Saint Vincent Healthcare
Billings, Montana, 59101, United States
Montana Cancer Consortium NCORP
Billings, Montana, 59102, United States
Saint Vincent Frontier Cancer Center
Billings, Montana, 59102, United States
Bozeman Deaconess Hospital
Bozeman, Montana, 59715, United States
Benefis Healthcare- Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Great Falls Clinic
Great Falls, Montana, 59405, United States
Saint Peter's Community Hospital
Helena, Montana, 59601, United States
Glacier Oncology PLLC
Kalispell, Montana, 59901, United States
Kalispell Regional Medical Center
Kalispell, Montana, 59901, United States
Saint Patrick Hospital - Community Hospital
Missoula, Montana, 59802, United States
CHI Health Good Samaritan
Kearney, Nebraska, 68847, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Saint Peter's University Hospital
New Brunswick, New Jersey, 08901, United States
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
Overlook Hospital
Summit, New Jersey, 07902, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Mission Hospital
Asheville, North Carolina, 28801, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Wayne Memorial Hospital
Goldsboro, North Carolina, 27534, United States
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, 28791, United States
Iredell Memorial Hospital
Statesville, North Carolina, 28677, United States
Southeast Clinical Oncology Research Consortium NCORP
Winston-Salem, North Carolina, 27104, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Cleveland Clinic Akron General
Akron, Ohio, 44307, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Saint Charles Health System
Bend, Oregon, 97701, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Penn State Children's Hospital
Hershey, Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
AnMed Health Hospital
Anderson, South Carolina, 29621, United States
Prisma Health Richland Hospital
Columbia, South Carolina, 29203, United States
Saint Francis Hospital
Greenville, South Carolina, 29601, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Greenville Cancer Treatment Center
Greenville, South Carolina, 29605, United States
Carolina Blood and Cancer Care Associates PA-Lancaster
Lancaster, South Carolina, 29720, United States
Spartanburg Medical Center
Spartanburg, South Carolina, 29303, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Driscoll Children's Hospital
Corpus Christi, Texas, 78411, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
Cancer Care Center at Island Hospital
Anacortes, Washington, 98221, United States
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, 98225, United States
Harrison HealthPartners Hematology and Oncology-Bremerton
Bremerton, Washington, 98310, United States
Highline Medical Center-Main Campus
Burien, Washington, 98166, United States
Kadlec Clinic Hematology and Oncology
Kennewick, Washington, 99336, United States
Skagit Valley Hospital
Mount Vernon, Washington, 98274, United States
Harrison HealthPartners Hematology and Oncology-Poulsbo
Poulsbo, Washington, 98370, United States
Harborview Medical Center
Seattle, Washington, 98104, United States
Minor and James Medical PLLC
Seattle, Washington, 98104, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Kaiser Permanente Washington
Seattle, Washington, 98112, United States
Swedish Medical Center-First Hill
Seattle, Washington, 98122-4307, United States
University of Washington Medical Center - Montlake
Seattle, Washington, 98195, United States
PeaceHealth United General Medical Center
Sedro-Woolley, Washington, 98284, United States
Cancer Care Northwest - Spokane South
Spokane, Washington, 99202, United States
Evergreen Hematology and Oncology PS
Spokane, Washington, 99218, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405, United States
Wenatchee Valley Hospital and Clinics
Wenatchee, Washington, 98801, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
Yakima, Washington, 98902, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Welch Cancer Center
Sheridan, Wyoming, 82801, United States
Royal Children's Hospital-Brisbane
Herston, Queensland, 4029, Australia
Queensland Children's Hospital
South Brisbane, Queensland, 4101, Australia
Princess Margaret Hospital for Children
Perth, Western Australia, 6008, Australia
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Jack M Su
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 25, 2010
First Posted
August 26, 2010
Study Start
August 9, 2010
Primary Completion
June 30, 2017
Study Completion
September 30, 2021
Last Updated
October 28, 2021
Results First Posted
March 3, 2020
Record last verified: 2021-10