Vorinostat and Radiation Therapy Followed By Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Pontine Glioma

This study has suspended participant recruitment.
(Temporarily Closed to Accrual)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01189266
First received: August 25, 2010
Last updated: June 30, 2014
Last verified: March 2014
  Purpose

This phase I/II trial is studying 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 pontine gliomas. 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.


Condition Intervention Phase
Childhood Mixed Glioma
Untreated Childhood Brain Stem Glioma
Drug: vorinostat
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Event-free survival [ Time Frame: From study enrollment to disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: August 2010
Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: vorinostat
Given PO or IV
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Radiation: 3-dimensional conformal radiation therapy
Undergo radiation
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Radiation: intensity-modulated radiation therapy
Undergo radiation
Other Name: IMRT

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01189266

  Hide Study Locations
Locations
United States, Alabama
Children's Hospital of Alabama
Birmingham, Alabama, United States, 35233
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Providence Hospital
Mobile, Alabama, United States, 36608
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Highlands Oncology Group-Rogers
Rogers, Arkansas, United States, 72758
United States, California
Kaiser Permanente-Deer Valley Medical Center
Antioch, California, United States, 94531
Southern California Permanente Medical Group
Downey, California, United States, 90242
Kaiser Permanente, Fremont
Fremont, California, United States, 94538
Kaiser Permanente
Fresno, California, United States, 93720
Miller Children's Hospital
Long Beach, California, United States, 90806
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Children's Hospital Central California
Madera, California, United States, 93636-8762
Contra Costa Regional Medical Center
Martinez, California, United States, 94553-3156
El Camino Hospital
Mountain View, California, United States, 94040
Highland General Hospital
Oakland, California, United States, 94602
Bay Area Tumor Institute CCOP
Oakland, California, United States, 94609
Kaiser Permanente-Oakland
Oakland, California, United States, 94611
Alta Bates Summit Medical Center - Summit Campus
Oakland, California, United States, 94609
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609-1809
Childrens Hospital of Orange County
Orange, California, United States, 92868-3874
Kaiser Permanente-Redwood City
Redwood City, California, United States, 94063
Kaiser Permanente-Richmond
Richmond, California, United States, 94801
Kaiser Permanente-Roseville
Roseville, California, United States, 95661
Kaiser Permanente - Sacramento
Sacramento, California, United States, 95825
Kaiser Permanente-South Sacramento
Sacramento, California, United States, 95823
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
Kaiser Permanente-San Francisco
San Francisco, California, United States, 94115
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California, United States, 95119
Kaiser Permanente San Leandro
San Leandro, California, United States, 94577
Doctors Medical Center- JC Robinson Regional Cancer Center
San Pablo, California, United States, 94806
Kaiser Permanente-San Rafael
San Rafael, California, United States, 94903
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, United States, 95051
Kaiser Permanente-Santa Rosa
Santa Rosa, California, United States, 95403
Kaiser Permanente-South San Francisco
South San Francisco, California, United States, 94080
Kaiser Permanente-Stockton
Stockton, California, United States, 95210
Kaiser Permanente Medical Center-Vacaville
Vacaville, California, United States, 95688
Kaiser Permanente-Vallejo
Vallejo, California, United States, 94589
Kaiser Permanente-Walnut Creek
Walnut Creek, California, United States, 94596
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Saint Francis Hospital and Medical Center
Hartford, Connecticut, United States, 06105
United States, Delaware
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
Lee Memorial Health System
Fort Myers, Florida, United States, 33901
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States, 32207
Florida Hospital
Orlando, Florida, United States, 32803
Nemours Children's Clinic - Orlando
Orlando, Florida, United States, 32806
UF Cancer Center at Orlando Health
Orlando, Florida, United States, 32806
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
Memorial Health University Medical Center
Savannah, Georgia, United States, 31403
United States, Hawaii
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, United States, 96819
University of Hawaii
Honolulu, Hawaii, United States, 96813
United States, Idaho
Saint Alphonsus Regional Medical Center
Boise, Idaho, United States, 83706
United States, Illinois
Saint Anthony's Health
Alton, Illinois, United States, 62002
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Good Samaritan Regional Health Center
Mount Vernon, Illinois, United States, 62864
Edward Hospital/Cancer Center
Naperville, Illinois, United States, 60540
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61602
Memorial Medical Center
Springfield, Illinois, United States, 62781-0001
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Iowa
Blank Children's Hospital
Des Moines, Iowa, United States, 50309
United States, Kentucky
Baptist Health Lexington
Lexington, Kentucky, United States, 40503
University of Kentucky
Lexington, Kentucky, United States, 40536
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, United States, 48106-0995
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Michigan Cancer Research Consortium Community Clinical Oncology Program
Ann Arbor, Michigan, United States, 48106
Oakwood Hospital
Dearborn, Michigan, United States, 48124
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Hurley Medical Center
Flint, Michigan, United States, 48502
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, United States, 48532
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
Allegiance Health
Jackson, Michigan, United States, 49201
Sparrow Hospital
Lansing, Michigan, United States, 48912
Saint Mary Mercy Hospital
Livonia, Michigan, United States, 48154
Saint Joseph Mercy Oakland
Pontiac, Michigan, United States, 48341-2985
Saint Joseph Mercy Port Huron
Port Huron, Michigan, United States, 48060
Saint Mary's of Michigan
Saginaw, Michigan, United States, 48601
Saint John Macomb-Oakland Hospital
Warren, Michigan, United States, 48093
United States, Minnesota
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
Singing River Hospital
Pascagoula, Mississippi, United States, 39581
United States, Missouri
Saint Francis Medical Center
Cape Girardeau, Missouri, United States, 63703
The Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
Cardinal Glennon Children's Medical Center
Saint Louis, Missouri, United States, 63104
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Saint Louis-Cape Girardeau CCOP
Saint Louis, Missouri, United States, 63141
Saint Louis Cancer and Breast Institute-South City
Saint Louis, Missouri, United States, 63109
Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield
Springfield, Missouri, United States, 65804
Mercy Hospital Springfield
Springfield, Missouri, United States, 65804
CoxHealth South Hospital
Springfield, Missouri, United States, 65807
United States, Montana
Billings Clinic
Billings, Montana, United States, 59107-7000
Hematology-Oncology Centers of the Northern Rockies PC
Billings, Montana, United States, 59102
Saint Vincent Healthcare
Billings, Montana, United States, 59101
Montana Cancer Consortium CCOP
Billings, Montana, United States, 59101
Bozeman Deaconess Cancer Center
Bozeman, Montana, United States, 59715
Bozeman Deaconess Hospital
Bozeman, Montana, United States, 59715
Benefis Healthcare- Sletten Cancer Institute
Great Falls, Montana, United States, 59405
Big Sky Oncology
Great Falls, Montana, United States, 59405
Great Falls Clinic
Great Falls, Montana, United States, 59405
Saint Peter's Community Hospital
Helena, Montana, United States, 59601
Kalispell Regional Medical Center
Kalispell, Montana, United States, 59901
Glacier Oncology PLLC
Kalispell, Montana, United States, 59901
Saint Patrick Hospital - Community Hospital
Missoula, Montana, United States, 59802
United States, Nebraska
Good Samaritan Hospital
Kearney, Nebraska, United States, 68847
United States, New Jersey
Morristown Memorial Hospital
Morristown, New Jersey, United States, 07962
Saint Peter's University Hospital
New Brunswick, New Jersey, United States, 08901
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
Overlook Hospital
Summit, New Jersey, United States, 07902
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
United States, New York
Montefiore Medical Center - Moses Campus
Bronx, New York, United States, 10467-2490
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Columbia University Medical Center
New York, New York, United States, 10032
New York University Langone Medical Center
New York, New York, United States, 10016
United States, North Carolina
Mission Hospital-Memorial Campus
Asheville, North Carolina, United States, 28801
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
Wayne Memorial Hospital
Goldsboro, North Carolina, United States, 27534
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, United States, 28791
Iredell Memorial Hospital
Statesville, North Carolina, United States, 28677
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Akron General Medical Center
Akron, Ohio, United States, 44307
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Saint Charles Medical Center-Bend
Bend, Oregon, United States, 97701
Oregon Health and Science University
Portland, Oregon, United States, 97239
Legacy Emanuel Children's Hospital
Portland, Oregon, United States, 97227
United States, Pennsylvania
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
AnMed Health Hospital
Anderson, South Carolina, United States, 29621
Palmetto Health Richland
Columbia, South Carolina, United States, 29203
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States, 29605
Greenville Cancer Treatment Center
Greenville, South Carolina, United States, 29605
Saint Francis Hospital
Greenville, South Carolina, United States, 29601
Carolina Blood and Cancer Care Associates PA-Lancaster
Lancaster, South Carolina, United States, 29720
Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
Upstate Carolina CCOP
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78411
Baylor College of Medicine
Houston, Texas, United States, 77030
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
United States, Utah
Primary Children's Hospital
Salt Lake City, Utah, United States, 84113
United States, Virginia
Childrens Hospital-King's Daughters
Norfolk, Virginia, United States, 23507
United States, Washington
Cancer Care Center at Island Hospital
Anacortes, Washington, United States, 98221
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, United States, 98225
Harrison HealthPartners Hematology and Oncology-Bremerton
Bremerton, Washington, United States, 98310
Highline Medical Center-Main Campus
Burien, Washington, United States, 98166
Columbia Basin Hematology and Oncology PLLC
Kennewick, Washington, United States, 99336
Skagit Valley Hospital
Mount Vernon, Washington, United States, 98274
Harrison HealthPartners Hematology and Oncology-Poulsbo
Poulsbo, Washington, United States, 98370
Group Health Cooperative-Seattle
Seattle, Washington, United States, 98112
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Harborview Medical Center
Seattle, Washington, United States, 98104
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Minor and James Medical PLLC
Seattle, Washington, United States, 98104
Swedish Medical Center-First Hill
Seattle, Washington, United States, 98122-4307
University of Washington Medical Center
Seattle, Washington, United States, 98195
United General Hospital
Sedro-Woolley, Washington, United States, 98284
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Evergreen Hematology and Oncology PS
Spokane, Washington, United States, 99218
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States, 98405
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
Yakima, Washington, United States, 98902
United States, Wisconsin
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
United States, Wyoming
Welch Cancer Center
Sheridan, Wyoming, United States, 82801
Australia, Queensland
Royal Childrens Hospital
Herston, Queensland, Australia, 4029
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6008
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
Investigators
Principal Investigator: Jack Su Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01189266     History of Changes
Other Study ID Numbers: NCI-2011-02600, NCI-2011-02600, CDR0000683459, COG-ACNS0927, ACNS0927, ACNS0927, U10CA098543, U01CA097452
Study First Received: August 25, 2010
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioma
Pontine Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Astrocytoma
Vorinostat
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 10, 2014