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Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00100802
Recruitment Status : Completed
First Posted : January 7, 2005
Results First Posted : January 13, 2017
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide and lomustine after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas.


Condition or disease Intervention/treatment Phase
Brain Tumors Central Nervous System Tumors Drug: lomustine Drug: temozolomide Procedure: adjuvant therapy Radiation: radiation therapy Phase 2

Detailed Description:

OBJECTIVES:

  • Compare event-free survival of pediatric patients with newly diagnosed high-grade gliomas treated with adjuvant radiotherapy and temozolomide followed by temozolomide and lomustine with historical controls.
  • Determine the toxicity of this regimen in these patients.
  • Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with this regimen.
  • Correlate polymorphisms in GSTP1, GSTM1, and GSTT1 genes and GSTP1 protein expression in tumors with survival in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

  • Chemoradiotherapy: Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47.
  • Maintenance chemotherapy: Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 50-100 patients will be accrued for this study within 1-1.5 years.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 118 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma
Study Start Date : July 2005
Actual Primary Completion Date : September 1, 2012
Actual Study Completion Date : June 30, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Surgery, Chemoradiotherapy, Rest, Maintenance, FUP
Patients must begin therapy within 31 days of surgery. Chemoradiotherapy = Radiation Therapy Dose: 54.0 Gy with a Boost of 5.4 Gy Temozolomide 90mg/m2/day daily for 42 days. Maintenance consists of 6 treatment cycles of combo chemotherapy with lomustine and temozolomide. Maintenance will begin 4 weeks following radiation. Five days of temozolomide (day 1 - 5) and one dose of lomustine (day 1) followed by 36 days of rest = 1 treatment cycle.
Drug: lomustine
Capsule
Other Names:
  • Ceenu
  • NSC #79037

Drug: temozolomide
Capsule
Other Names:
  • Temodar
  • NSC # 362856

Procedure: adjuvant therapy
Radiation: radiation therapy



Primary Outcome Measures :
  1. One Year Overall Survival [ Time Frame: One year ]
    Estimated one year survival using the Kaplan-Meier methodology.

  2. Occurrence of Death Attributable to Complications of Protocol Therapy [ Time Frame: While receiving protocol therapy (up to 301 days excluding delays) or within 30 days of Termination of Protocol Therapy ]
    Number of deaths due to complications of protocol therapy.



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed, newly diagnosed high-grade glioma of 1 of the following histologies:

    • Anaplastic astrocytoma
    • Glioblastoma multiforme
    • Gliosarcoma
  • Primary spinal cord malignant gliomas allowed
  • No primary brainstem tumors
  • Has undergone surgical resection or biopsy of the tumor within the past 31 days

    • Pre-operative and post-operative brain MRI with and without gadolinium-contrast OR pre-operative and post-operative spine MRI for spinal cord primaries

      • Post-operative MRI not required for patients who undergo biopsy only
  • No evidence of neuraxis dissemination

    • Spine MRI and cerebrospinal fluid cytology required only if clinically indicated

PATIENT CHARACTERISTICS:

Age

  • 3 to 21

Performance status

  • Karnofsky 50-100% (for patients > 16 years of age)
  • Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

  • At least 8 weeks

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 8 g/dL (transfusions allowed)

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 2.5 times ULN
  • Albumin ≥ 2 g/dL

Renal

  • Creatinine ≤ 1.5 times ULN OR
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of normal

Pulmonary

  • No evidence of dyspnea at rest
  • No exercise intolerance
  • Pulse oximetry ≥ 94% (if determination is clinically indicated)

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after study participation
  • Able to swallow oral medication
  • Seizures allowed provided they are well controlled with anticonvulsants
  • No hypersensitivity to temozolomide

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior biologic agents

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • Prior corticosteroids allowed
  • No concurrent corticosteroids as an antiemetic
  • Concurrent corticosteroids allowed only for treatment of increased intracranial pressure

Radiotherapy

  • No concurrent radiotherapy using cobalt-60

Surgery

  • See Disease Characteristics

Other

  • No other prior treatment
  • No concurrent phenobarbital or cimetidine
  • No concurrent co-trimoxazole for Pneumocystis carinii pneumonia prophylaxis during study chemoradiotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00100802


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Locations
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United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016-7710
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242-2814
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States, 90801
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048-1865
Children's Hospital & Research Center Oakland
Oakland, California, United States, 94609-1809
Children's Hospital of Orange County
Orange, California, United States, 92868
Sutter Cancer Center
Sacramento, California, United States, 95816
University of California Davis Cancer Center
Sacramento, California, United States, 95817
Kaiser Permanente Medical Center - Oakland
Sacramento, California, United States, 95825
Children's Hospital and Health Center - San Diego
San Diego, California, United States, 92123-4282
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
Stanford Comprehensive Cancer Center - Stanford
Stanford, California, United States, 94305
United States, Colorado
Children's Hospital Cancer Center
Denver, Colorado, United States, 80218-1088
United States, Connecticut
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
Farmington, Connecticut, United States, 06360-2875
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19899
United States, Florida
Broward General Medical Center Cancer Center
Fort Lauderdale, Florida, United States, 33316
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States, 33901
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
Miami Children's Hospital
Miami, Florida, United States, 33155
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola, Florida, United States, 32504
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States, 33407
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
MBCCOP - Medical College of Georgia Cancer Center
Augusta, Georgia, United States, 30912-3730
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Advocate Christ Medical Center
Oak Lawn, Illinois, United States, 60453
Advocate Lutheran General Cancer Care Center
Park Ridge, Illinois, United States, 60068-1174
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61637
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62794-9620
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
St. Vincent Indianapolis Hospital
Indianapolis, Indiana, United States, 46260
United States, Iowa
Blank Children's Hospital
Des Moines, Iowa, United States, 50309
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
United States, Kentucky
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536-0293
Kosair Children's Hospital
Louisville, Kentucky, United States, 40232
United States, Louisiana
Tulane Cancer Center Office of Clinical Research
Alexandria, Louisiana, United States, 71315-3198
Ochsner Cancer Institute at Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Maine
CancerCare of Maine at Eastern Maine Medial Center
Bangor, Maine, United States, 04401
Maine Children's Cancer Program at Barbara Bush Children's Hospital
Scarborough, Maine, United States, 04074-9308
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Hurley Medical Center
Flint, Michigan, United States, 48503
Spectrum Health Hospital - Butterworth Campus
Grand Rapids, Michigan, United States, 49503-2560
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States, 48236
Breslin Cancer Center at Ingham Regional Medical Center
Lansing, Michigan, United States, 48910
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
University of Minnesota Children's Hospital - Fairview
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Cancer Clinic
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, United States, 65203
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Cardinal Glennon Children's Hospital
Saint Louis, Missouri, United States, 63104
Siteman Cancer Center at Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Children's Hospital
Omaha, Nebraska, United States, 68114-4113
United States, Nevada
Sunrise Hospital and Medical Center
Las Vegas, Nevada, United States, 89109-2306
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
Overlook Hospital
Morristown, New Jersey, United States, 07962
Saint Peter's University Hospital
New Brunswick, New Jersey, United States, 08901
St. Joseph's Hospital and Medical Center
Paterson, New Jersey, United States, 07503
United States, New Mexico
University of New Mexico Cancer Research and Treatment Center
Albuquerque, New Mexico, United States, 87131-5636
United States, New York
Albany Medical Center Hospital
Albany, New York, United States, 12208-3419
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Brooklyn Hospital Center
Brooklyn, New York, United States, 11201-5493
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Winthrop University Hospital
Mineola, New York, United States, 11501
Schneider Children's Hospital
New Hyde Park, New York, United States, 11040
NYU Cancer Institute at New York University Medical Center
New York, New York, United States, 10016
Memorial Sloan - Kettering Cancer Center
New York, New York, United States, 10021-6094
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States, 10032
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233-3549
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, North Dakota
CCOP - MeritCare Hospital
Fargo, North Dakota, United States, 58122
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308-1062
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-5000
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195-5217
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404-1815
Toledo Hospital
Toledo, Ohio, United States, 43606
Tod Children's Hospital
Youngstown, Ohio, United States, 44501
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Legacy Emanuel Hospital and Health Center & Children's Hospital
Portland, Oregon, United States, 97227
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134-1095
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Rhode Island Hospital Comprehensive Cancer Center
Providence, Rhode Island, United States, 02903
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Palmetto Health South Carolina Cancer Center
Columbia, South Carolina, United States, 29203
United States, South Dakota
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, United States, 57117-5039
United States, Tennessee
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37901
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Tech University Health Sciences Center School of Medicine - Amarillo
Amarillo, Texas, United States, 79106
Children's Hospital of Austin
Austin, Texas, United States, 78701
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78411
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104-9958
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030-2399
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78207
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229-3993
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113-1100
United States, Vermont
Fletcher Allen Health Care - University Health Center Campus
Burlington, Vermont, United States, 05405
United States, Virginia
INOVA Fairfax Hospital
Fairfax, Virginia, United States, 22031
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States, 23507-1971
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Carilion Cancer Center of Western Virginia
Roanoke, Virginia, United States, 24029
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Providence Cancer Center at Sacred Heart Medical Center
Spokane, Washington, United States, 99220-2555
Madigan Army Medical Center - Tacoma
Tacoma, Washington, United States, 98431
United States, West Virginia
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
Huntington, West Virginia, United States, 25701
United States, Wisconsin
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
John Hunter Hospital
Newcastle, New South Wales, Australia, 2310
Westmead Institute for Cancer Research at Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Royal Children's Hospital
Herston, Brisbane, Queensland, Australia, 4029
Australia, South Australia
Women's and Children's Hospital
North Adelaide, South Australia, Australia, 5006
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, Alberta
CHUS-Hopital Fleurimont
Sherbrooke, Alberta, Canada, J1H5N4
Canada, British Columbia
Children's & Women's Hospital of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3K 6R8
Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 3N6
Children's Hospital of Western Ontario
London, Ontario, Canada, N6A 4G5
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Canada, Saskatchewan
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Canada
Centre Hospitalier Universitaire de Quebec
Quebec, Canada, G1V 4G2
New Zealand
Starship Children's Health
Auckland, New Zealand, 1
Christchurch Hospital
Christchurch, New Zealand
Wellington Children's Hospital
Wellington, New Zealand, 6002
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Switzerland
Swiss Pediatric Oncology Group Geneva
Geneva, Switzerland, 1205
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
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Study Chair: Regina Jakacki, MD University of Pittsburgh

Publications of Results:
Other Publications:
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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00100802     History of Changes
Other Study ID Numbers: ACNS0423
CDR0000407744 ( Other Identifier: Clinical Trials.gov )
COG-ACNS0423 ( Other Identifier: Children's Oncology Group )
NCI-2012-02645 ( Other Identifier: Registry ID: CTRP (Clinical Trial Reporting Program) )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: January 7, 2005    Key Record Dates
Results First Posted: January 13, 2017
Last Update Posted: August 7, 2019
Last Verified: November 2016
Keywords provided by Children's Oncology Group:
childhood high-grade cerebral astrocytoma
childhood spinal cord neoplasm
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Temozolomide
Lomustine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents