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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)

Phase 1/Phase 2
3 Years
21 Years
Open (Enrolling)
Childhood Mixed Glioma, Untreated Childhood Brain Stem Glioma

Thank you

Trial Information

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)


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.


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

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.

Inclusion Criteria:

- Newly diagnosed diffuse intrinsic pontine gliomas (defined as tumors with a pontine
epicenter and diffuse involvement of ≥ 2/3 of the pons)

- Patients with brainstem tumors that do not meet these criteria or are not
considered to be typical intrinsic pontine gliomas are eligible provided their
tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma
multiforme, gliosarcoma, or anaplastic mixed glioma

- No patients with juvenile pilocytic astrocytoma, fibrillary astrocytoma,
gangliogliomas, or other mixed gliomas without anaplasia

- No patients with disseminated disease (MRI of the spine must be performed if
disseminated disease is suspected by the treating physician)

- Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) or Lansky
PS 50-100% (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 status

- ANC ≥ 1,000/uL

- Platelet count ≥ 100,000/uL (transfusion independent, defined as not receiving
platelet transfusions within the past 7 days)

- Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)

- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on
age/gender as follows:

- ≤ 0.8 mg/dL (for patients 3 to < 6 years of age)

- ≤ 1 mg/dL (for patients 6 to < 10 years of age)

- ≤ 1.2 mg/dL (for patients 10 to < 13 years of age)

- ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)

- ≤ 1.5 mg/dL (for male patients 13 to < 16 years of age)

- ≤ 1.7 mg/dL (for male patients ≥ 16 years of age)

- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit of normal (ULN)
for age

- ALT ≤ 110 U/L (for the purpose of this study, the ULN for ALT is 45 U/L)

- Serum albumin ≥ 2 g/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to swallow capsules or liquids

- Not dependent on NG tube feeding

- Patients with seizure disorder are eligible provided that they are not on
enzyme-inducing anticonvulsants and seizures are well controlled

- No uncontrolled infection

- No patients who, in the opinion of the investigator, may not be able to comply with
the safety monitoring requirements of the study

- No prior treatment except for dexamethasone and/or surgery

- At least 2 weeks since prior valproic acid

- More than 7 days since prior growth factors that support platelet or white cell
number or function

- No other concurrent investigational drugs

- No other concurrent anticancer agents (including chemotherapy, immunotherapy, or
biologic therapy)

- No concurrent coumadin, heparin, low-molecular weight heparin, or any other

- No concurrent aspirin (> 81 mg/day), NSAIDs, clopidogrel (Plavix), dipyridamole
(Persantine), or any other drug that inhibits platelet function

- No concurrent enzyme-inducing anticonvulsants

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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)

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Jack Su

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

August 2010

Completion Date:

Related Keywords:

  • Childhood Mixed Glioma
  • Untreated Childhood Brain Stem Glioma
  • Glioma
  • Pontine Glioma



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