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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)
Both
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)


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.


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
anticoagulants

- 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:

Interventional

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:

Yes

Principal Investigator

Jack Su

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02600

NCT ID:

NCT01189266

Start Date:

August 2010

Completion Date:

Related Keywords:

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

Name

Location

Baylor College of MedicineHouston, Texas  77030
Roswell Park Cancer InstituteBuffalo, New York  14263
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
University of Washington Medical CenterSeattle, Washington  98195-6043
Hurley Medical CenterFlint, Michigan  48503
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Loyola University Medical CenterMaywood, Illinois  60153
Morristown Memorial HospitalMorristown, New Jersey  07962-1956
Akron General Medical CenterAkron, Ohio  44302
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Cedars-Sinai Medical CenterLos Angeles, California  90048
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Children's National Medical CenterWashington, District of Columbia  20010-2970
Kaiser Permanente Medical Center - Santa ClaraSanta Clara, California  95051-5386
All Children's HospitalSt. Petersburg, Florida  33701
Saint Jude Midwest AffiliatePeoria, Illinois  61637
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Group Health CooperativeSeattle, Washington  98112
Great Falls ClinicGreat Falls, Montana  59405
Overlook HospitalSummit, New Jersey  07902-0220
Central Baptist HospitalLexington, Kentucky  40503
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Montefiore Medical CenterBronx, New York  10467-2490
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
Bozeman Deaconess HospitalBozeman, Montana  59715
Big Sky OncologyGreat Falls, Montana  59405
Kalispell Regional Medical CenterKalispell, Montana  59901
Harborview Medical CenterSeattle, Washington  98104
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
Welch Cancer CenterSheridan, Wyoming  82801
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Children's Hospital and Research Center at OaklandOakland, California  94609-1809
Mary Bridge Children's Hospital and Health CenterTacoma, Washington  98415-0299
Alta Bates Summit Medical Center - Summit CampusOakland, California  94609
Saint Francis Medical CenterCape Girardeau, Missouri  63701
Iredell Memorial HospitalStatesville, North Carolina  28677
North Star Lodge Cancer Center at Yakima Valley Memorial HospitalYakima, Washington  98902
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Highland General HospitalOakland, California  94602
Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
Wenatchee Valley Medical CenterWenatchee, Washington  98801-2028
Singing River HospitalPascagoula, Mississippi  39581
Memorial Medical CenterSpringfield, Illinois  62781
Lee Memorial Health SystemFort Myers, Florida  33902
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Providence HospitalMobile, Alabama  36608
Children's Hospital of AlabamaBirmingham, Alabama  35233
Vanderbilt UniversityNashville, Tennessee  37232-6305
Contra Costa Regional Medical CenterMartinez, California  94553-3156
Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Nemours Children's Clinic - PensacolaPensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum HealthGrand Rapids, Michigan  49503
El Camino HospitalMountain View, California  94040
Legacy Emanuel Children's HospitalPortland, Oregon  97227
Kaiser PermanenteSacramento, California  
University of KentuckyLexington, Kentucky  40536-0098
Montana Cancer Consortium CCOPBillings, Montana  59101
Oregon Health and Science UniversityPortland, Oregon  97201
Decatur Memorial HospitalDecatur, Illinois  62526
Florida HospitalOrlando, Florida  32803
Memorial Health University Medical CenterSavannah, Georgia  31404
Seattle Children's HospitalSeattle, Washington  98105
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Childrens Memorial HospitalChicago, Illinois  60614
Highlands Oncology Group-BentonvilleBentonville, Arkansas  72712
Kaiser Permanente, FremontFremont, California  94538
Kaiser Permanente, HaywardHayward, California  94545
Bay Area Tumor Institution CCOPOakland, California  94609
Kaiser Permanente-OaklandOakland, California  94611
Kaiser Permanente-Redwood CityRedwood City, California  94063
Kaiser Permanente-RichmondRichmond, California  94801
Kaiser Permanente-RosevilleRoseville, California  95661
Kaiser Permanente-South SacramentoSacramento, California  95823
Kaiser Permanente - SacramentoSacramento, California  95825
Kaiser Permanente-San FranciscoSan Francisco, California  94115
Kaiser Permanente-Santa Teresa-San JoseSan Jose, California  95119
Doctors Medical Center- JC Robinson Regional Cancer CenterSan Pablo, California  94806
Kaiser Permanente-San RafaelSan Rafael, California  94903
Kaiser Permanente-Santa RosaSanta Rosa, California  95403
Kaiser Permanente-South San FranciscoSouth San Francisco, California  94080
Kaiser Permanente-StocktonStockton, California  95210
Kaiser Permanente-VallejoVallejo, California  94589
Kaiser Permanente-Walnut CreekWalnut Creek, California  94596
Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
University of HawaiiHonolulu, Hawaii  96813
Saint Anthony's HealthAlton, Illinois  62002
Good Samaritan Regional Medical CenterMt. Vernon, Illinois  62864
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Saint Louis-Cape Girardeau CCOPSaint Louis, Missouri  63141
Ozark Health Ventures LLC dba Cancer Research for The Ozarks SpringfieldSpringfield, Missouri  65802
Saint John's HospitalSpringfield, Missouri  65804
Cox Medical CenterSpringfield, Missouri  65807
Hematology-Oncology Centers of the Northern Rockies PCBillings, Montana  59101
Saint Vincent HealthcareBillings, Montana  59101
Billings ClinicBillings, Montana  59107-7000
Benefis Healthcare- Sletten Cancer InstituteGreat Falls, Montana  59405
Saint Peter's Community HospitalHelena, Montana  59601
Glacier Oncology PLLCKalispell, Montana  59901
Saint Patrick Hospital - Community HospitalMissoula, Montana  59802
Good Samaritan HospitalKearney, Nebraska  68847
New York University Langone Medical CenterNew York, New York  10016
Columbia University Medical CenterNew York, New York  10032
Mission Hospitals IncAsheville, North Carolina  28801
Wayne Memorial HospitalGoldsboro, North Carolina  27534
Margaret R Pardee Memorial HospitalHendersonville, North Carolina  28791
AnMed Health HospitalAnderson, South Carolina  29621
Upstate Carolina CCOPSpartanburg, South Carolina  29303
Harrison Bremerton Hematology and OncologyBremerton, Washington  98310
Columbia Basin Hematology and Oncology PLLCKennewick, Washington  99336
Minor and James Medical PLLCSeattle, Washington  98104
Swedish Medical Center-First HillSeattle, Washington  98122-4307
Skagit Valley HospitalMt. Vernon, Washington  98273
Evergreen Hematology and Oncology PSSpokane, Washington  99218
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
Kaiser Permanente-Deer Valley Medical CenterAntioch, California  94531
Kaiser Permanente Medical Center-VacavilleVacaville, California  95688
Kaiser Permanente Moanalua Medical CenterHonolulu, Hawaii  96819
Saint Charles Medical Center-BendBend, Oregon  97701
Saint Francis HospitalGreenville, South Carolina  29601
Cancer Care Center at Island HospitalAnacortes, Washington  98221
Highline Medical Center-Main CampusBurien, Washington  98166
United General HospitalSedro-Woolley, Washington  98284
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Riley Hospital for ChildrenIndianapolis, Indiana  46202
Cardinal Glennon Children's Medical CenterSt. Louis, Missouri  63104
Miller Children's HospitalLong Beach, California  90806
Childrens Hospital of Orange CountyOrange, California  92868-3874
Alfred I duPont Hospital for ChildrenWilmington, Delaware  19803
Nemours Children's Clinic - JacksonvilleJacksonville, Florida  32207-8426
Nemours Childrens Clinic - OrlandoOrlando, Florida  32806
Children's Healthcare of Atlanta - EglestonAtlanta, Georgia  30322
The Childrens Mercy HospitalKansas City, Missouri  64108
Penn State Hershey Children's HospitalHershey, Pennsylvania  17033
Palmetto Health RichlandColumbia, South Carolina  29203
Childrens Hospital-King's DaughtersNorfolk, Virginia  23507
University of California San Francisco Medical Center-ParnassusSan Francisco, California  94143
Raymond Blank Children's HospitalDes Moines, Iowa  50309
Greenville Cancer Treatment CenterGreenville, South Carolina  29605
Genesys Regional Medical Center-West Flint CampusFlint, Michigan  48532
PeaceHealth Saint Joseph Medical CenterBellingham, Washington  98225
Edward Hospital/Cancer CenterNaperville, Illinois  60540
Saint Louis Cancer and Breast Institute-South CitySaint Louis, Missouri  63109
Harrison Poulsbo Hematology and OncologyPoulsbo, Washington  98370
Carolina Blood and Cancer Care Associates PA-LancasterLancaster, South Carolina  29720