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)
PRIMARY OBJECTIVES:
l. To estimate the maximum-tolerated dose (MTD) or recommend a phase II dose of vorinostat
given concurrently with radiotherapy in pediatric patients with newly diagnosed intrinsic
pontine gliomas.
II. To define and describe the toxicities of vorinostat given concurrently with radiotherapy
in these patients.
III. To determine, in the context of a this phase I/II trial, the antitumor activity of
combining vorinostat with radiotherapy followed by maintenance vorinostat for 12 courses in
these patients, as measured by 12-month event-free survival and overall survival.
IV. To determine the toxicities of vorinostat for 12 additional courses after completion of
concurrent vorinostat and radiotherapy.
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 radiotherapy, and
at the end of radiotherapy.
II. To measure HDAC2 levels and assess histone acetylation in PBMCs before treatment, at 2
weeks after starting vorinostat and radiotherapy, and at the end of radiotherapy.
III. To quantify DNA repair proteins from the NHEJ and homologous recombination repair
pathways in tumors by either Western analysis or IHC, if paraffin-embedded tumor is
available.
OUTLINE: This is a multicenter, phase I, dose-escalation study of vorinostat followed by a
phase II study.
Patients receive vorinostat orally or IV on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40.
Patients undergo 3D-conformal or intensity-modulated radiotherapy 5 days per week for 6
weeks. Patients then receive maintenance therapy comprising oral vorinostat on days 1-28.
Treatment repeats every 28 days for 12 courses in the absence of disease progression or
unacceptable toxicity.
Blood and tumor samples may be collected periodically for correlative studies.
After completion of study treatment, patients are followed up for up to 5 years.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of vorinostat in combination with radiation therapy determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)
28 days
Yes
Jack Su
Principal Investigator
Children's Oncology Group
United States: Food and Drug Administration
NCI-2011-02600
NCT01189266
August 2010
Name | Location |
---|---|
Baylor College of Medicine | Houston, Texas 77030 |
Roswell Park Cancer Institute | Buffalo, New York 14263 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
Washington University School of Medicine | Saint Louis, Missouri 63110 |
University of Washington Medical Center | Seattle, Washington 98195-6043 |
Hurley Medical Center | Flint, Michigan 48503 |
Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
Loyola University Medical Center | Maywood, Illinois 60153 |
Morristown Memorial Hospital | Morristown, New Jersey 07962-1956 |
Akron General Medical Center | Akron, Ohio 44302 |
Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
Cedars-Sinai Medical Center | Los Angeles, California 90048 |
University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
Kaiser Permanente Medical Center - Santa Clara | Santa Clara, California 95051-5386 |
All Children's Hospital | St. Petersburg, Florida 33701 |
Saint Jude Midwest Affiliate | Peoria, Illinois 61637 |
Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
Southern California Permanente Medical Group | Downey, California 90242 |
Children's Hospital Central California | Madera, California 93638-8762 |
Kosair Children's Hospital | Louisville, Kentucky 40202-3830 |
Group Health Cooperative | Seattle, Washington 98112 |
Great Falls Clinic | Great Falls, Montana 59405 |
Overlook Hospital | Summit, New Jersey 07902-0220 |
Central Baptist Hospital | Lexington, Kentucky 40503 |
Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle, Washington 98109 |
Montefiore Medical Center | Bronx, New York 10467-2490 |
Saint Peter's University Hospital | New Brunswick, New Jersey 08901-1780 |
Bozeman Deaconess Hospital | Bozeman, Montana 59715 |
Big Sky Oncology | Great Falls, Montana 59405 |
Kalispell Regional Medical Center | Kalispell, Montana 59901 |
Harborview Medical Center | Seattle, Washington 98104 |
Cancer Care Northwest - Spokane South | Spokane, Washington 99202 |
Welch Cancer Center | Sheridan, Wyoming 82801 |
Rady Children's Hospital - San Diego | San Diego, California 92123-4282 |
University of New Mexico Cancer Center | Albuquerque, New Mexico 87131-5636 |
Nationwide Children's Hospital | Columbus, Ohio 43205-2696 |
Children's Hospital and Research Center at Oakland | Oakland, California 94609-1809 |
Mary Bridge Children's Hospital and Health Center | Tacoma, Washington 98415-0299 |
Alta Bates Summit Medical Center - Summit Campus | Oakland, California 94609 |
Saint Francis Medical Center | Cape Girardeau, Missouri 63701 |
Iredell Memorial Hospital | Statesville, North Carolina 28677 |
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital | Yakima, Washington 98902 |
Saint Joseph Mercy Hospital | Ann Arbor, Michigan 48106 |
Highland General Hospital | Oakland, California 94602 |
Spartanburg Regional Medical Center | Spartanburg, South Carolina 29303 |
Bozeman Deaconess Cancer Center | Bozeman, Montana 59715 |
Wenatchee Valley Medical Center | Wenatchee, Washington 98801-2028 |
Singing River Hospital | Pascagoula, Mississippi 39581 |
Memorial Medical Center | Springfield, Illinois 62781 |
Lee Memorial Health System | Fort Myers, Florida 33902 |
University of Alabama at Birmingham | Birmingham, Alabama 35294-3300 |
Providence Hospital | Mobile, Alabama 36608 |
Children's Hospital of Alabama | Birmingham, Alabama 35233 |
Vanderbilt University | Nashville, Tennessee 37232-6305 |
Contra Costa Regional Medical Center | Martinez, California 94553-3156 |
Saint Alphonsus Regional Medical Center | Boise, Idaho 83706 |
Nemours Children's Clinic - Pensacola | Pensacola, Florida 32504 |
Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids, Michigan 49503 |
El Camino Hospital | Mountain View, California 94040 |
Legacy Emanuel Children's Hospital | Portland, Oregon 97227 |
Kaiser Permanente | Sacramento, California |
University of Kentucky | Lexington, Kentucky 40536-0098 |
Montana Cancer Consortium CCOP | Billings, Montana 59101 |
Oregon Health and Science University | Portland, Oregon 97201 |
Decatur Memorial Hospital | Decatur, Illinois 62526 |
Florida Hospital | Orlando, Florida 32803 |
Memorial Health University Medical Center | Savannah, Georgia 31404 |
Seattle Children's Hospital | Seattle, Washington 98105 |
Wake Forest University Health Sciences | Winston-Salem, North Carolina 27157 |
Childrens Memorial Hospital | Chicago, Illinois 60614 |
Highlands Oncology Group-Bentonville | Bentonville, Arkansas 72712 |
Kaiser Permanente, Fremont | Fremont, California 94538 |
Kaiser Permanente, Hayward | Hayward, California 94545 |
Bay Area Tumor Institution CCOP | Oakland, California 94609 |
Kaiser Permanente-Oakland | Oakland, California 94611 |
Kaiser Permanente-Redwood City | Redwood City, California 94063 |
Kaiser Permanente-Richmond | Richmond, California 94801 |
Kaiser Permanente-Roseville | Roseville, California 95661 |
Kaiser Permanente-South Sacramento | Sacramento, California 95823 |
Kaiser Permanente - Sacramento | Sacramento, California 95825 |
Kaiser Permanente-San Francisco | San Francisco, California 94115 |
Kaiser Permanente-Santa Teresa-San Jose | San Jose, California 95119 |
Doctors Medical Center- JC Robinson Regional Cancer Center | San Pablo, California 94806 |
Kaiser Permanente-San Rafael | San Rafael, California 94903 |
Kaiser Permanente-Santa Rosa | Santa Rosa, California 95403 |
Kaiser Permanente-South San Francisco | South San Francisco, California 94080 |
Kaiser Permanente-Stockton | Stockton, California 95210 |
Kaiser Permanente-Vallejo | Vallejo, California 94589 |
Kaiser Permanente-Walnut Creek | Walnut Creek, California 94596 |
Saint Francis Hospital and Medical Center | Hartford, Connecticut 06105 |
University of Hawaii | Honolulu, Hawaii 96813 |
Saint Anthony's Health | Alton, Illinois 62002 |
Good Samaritan Regional Medical Center | Mt. Vernon, Illinois 62864 |
Michigan Cancer Research Consortium Community Clinical Oncology Program | Ann Arbor, Michigan 48106 |
Oakwood Hospital | Dearborn, Michigan 48123 |
Saint John Hospital and Medical Center | Detroit, Michigan 48236 |
Allegiance Health | Jackson, Michigan 49201 |
Sparrow Hospital | Lansing, Michigan 48912 |
Saint Mary Mercy Hospital | Livonia, Michigan 48154 |
Saint Joseph Mercy Oakland | Pontiac, Michigan 48341-2985 |
Saint Joseph Mercy Port Huron | Port Huron, Michigan 48060 |
Saint Mary's of Michigan | Saginaw, Michigan 48601 |
Saint John Macomb-Oakland Hospital | Warren, Michigan 48093 |
Saint Louis-Cape Girardeau CCOP | Saint Louis, Missouri 63141 |
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield | Springfield, Missouri 65802 |
Saint John's Hospital | Springfield, Missouri 65804 |
Cox Medical Center | Springfield, Missouri 65807 |
Hematology-Oncology Centers of the Northern Rockies PC | Billings, Montana 59101 |
Saint Vincent Healthcare | Billings, Montana 59101 |
Billings Clinic | Billings, Montana 59107-7000 |
Benefis Healthcare- Sletten Cancer Institute | Great Falls, Montana 59405 |
Saint Peter's Community Hospital | Helena, Montana 59601 |
Glacier Oncology PLLC | Kalispell, Montana 59901 |
Saint Patrick Hospital - Community Hospital | Missoula, Montana 59802 |
Good Samaritan Hospital | Kearney, Nebraska 68847 |
New York University Langone Medical Center | New York, New York 10016 |
Columbia University Medical Center | New York, New York 10032 |
Mission Hospitals Inc | Asheville, North Carolina 28801 |
Wayne Memorial Hospital | Goldsboro, North Carolina 27534 |
Margaret R Pardee Memorial Hospital | Hendersonville, North Carolina 28791 |
AnMed Health Hospital | Anderson, South Carolina 29621 |
Upstate Carolina CCOP | Spartanburg, South Carolina 29303 |
Harrison Bremerton Hematology and Oncology | Bremerton, Washington 98310 |
Columbia Basin Hematology and Oncology PLLC | Kennewick, Washington 99336 |
Minor and James Medical PLLC | Seattle, Washington 98104 |
Swedish Medical Center-First Hill | Seattle, Washington 98122-4307 |
Skagit Valley Hospital | Mt. Vernon, Washington 98273 |
Evergreen Hematology and Oncology PS | Spokane, Washington 99218 |
University of Minnesota Medical Center-Fairview | Minneapolis, Minnesota 55455 |
Kaiser Permanente-Deer Valley Medical Center | Antioch, California 94531 |
Kaiser Permanente Medical Center-Vacaville | Vacaville, California 95688 |
Kaiser Permanente Moanalua Medical Center | Honolulu, Hawaii 96819 |
Saint Charles Medical Center-Bend | Bend, Oregon 97701 |
Saint Francis Hospital | Greenville, South Carolina 29601 |
Cancer Care Center at Island Hospital | Anacortes, Washington 98221 |
Highline Medical Center-Main Campus | Burien, Washington 98166 |
United General Hospital | Sedro-Woolley, Washington 98284 |
C S Mott Children's Hospital | Ann Arbor, Michigan 48109 |
Riley Hospital for Children | Indianapolis, Indiana 46202 |
Cardinal Glennon Children's Medical Center | St. Louis, Missouri 63104 |
Miller Children's Hospital | Long Beach, California 90806 |
Childrens Hospital of Orange County | Orange, California 92868-3874 |
Alfred I duPont Hospital for Children | Wilmington, Delaware 19803 |
Nemours Children's Clinic - Jacksonville | Jacksonville, Florida 32207-8426 |
Nemours Childrens Clinic - Orlando | Orlando, Florida 32806 |
Children's Healthcare of Atlanta - Egleston | Atlanta, Georgia 30322 |
The Childrens Mercy Hospital | Kansas City, Missouri 64108 |
Penn State Hershey Children's Hospital | Hershey, Pennsylvania 17033 |
Palmetto Health Richland | Columbia, South Carolina 29203 |
Childrens Hospital-King's Daughters | Norfolk, Virginia 23507 |
University of California San Francisco Medical Center-Parnassus | San Francisco, California 94143 |
Raymond Blank Children's Hospital | Des Moines, Iowa 50309 |
Greenville Cancer Treatment Center | Greenville, South Carolina 29605 |
Genesys Regional Medical Center-West Flint Campus | Flint, Michigan 48532 |
PeaceHealth Saint Joseph Medical Center | Bellingham, Washington 98225 |
Edward Hospital/Cancer Center | Naperville, Illinois 60540 |
Saint Louis Cancer and Breast Institute-South City | Saint Louis, Missouri 63109 |
Harrison Poulsbo Hematology and Oncology | Poulsbo, Washington 98370 |
Carolina Blood and Cancer Care Associates PA-Lancaster | Lancaster, South Carolina 29720 |