A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma
Phase 2
3 Years
21 Years
3 Years
21 Years
Not Enrolling
Both
Brain and Central Nervous System Tumors
Both
Brain and Central Nervous System Tumors
Trial Information
A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Event-free survival
Outcome Time Frame:
Time to disease progression, disease relapse, occurence of a second malignant neoplasm, or death from any cause assessed at 1 year
Safety Issue:
No
Principal Investigator
Regina Jakacki, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Children's Hospital of Pittsburgh of UPMC
Authority:
United States: Federal Government
Study ID:
ACNS0423
NCT ID:
NCT00100802
Start Date:
March 2005
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- childhood high-grade cerebral astrocytoma
- childhood spinal cord neoplasm
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| Hurley Medical Center | Flint, Michigan 48503 |
| Medical City Dallas Hospital | Dallas, Texas 75230 |
| University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
| Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
| Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center | Farmington, Connecticut 06360-2875 |
| Van Elslander Cancer Center at St. John Hospital and Medical Center | Grosse Pointe Woods, Michigan 48236 |
| CCOP - MeritCare Hospital | Fargo, North Dakota 58122 |
| Penn State Cancer Institute at Milton S. Hershey Medical Center | Hershey, Pennsylvania 17033-0850 |
| Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls, South Dakota 57117-5039 |
| Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
| New York Medical College | Valhalla, New York 10595 |
| Holden Comprehensive Cancer Center at University of Iowa | Iowa City, Iowa 52242-1002 |
| Ellis Fischel Cancer Center at University of Missouri - Columbia | Columbia, Missouri 65203 |
| Siteman Cancer Center at Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
| CCOP - Scott and White Hospital | Temple, Texas 76508 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
| Sutter Cancer Center | Sacramento, California 95816 |
| Children's Hospital of Orange County | Orange, California 92668 |
| Children's Mercy Hospital | Kansas City, Missouri 64108 |
| St. Joseph's Hospital and Medical Center | Paterson, New Jersey 07503 |
| Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
| University of California Davis Cancer Center | Sacramento, California 95817 |
| Miami Children's Hospital | Miami, Florida 33155-4069 |
| All Children's Hospital | St. Petersburg, Florida 33701 |
| Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
| Saint Jude Midwest Affiliate | Peoria, Illinois 61637 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
| Cardinal Glennon Children's Hospital | Saint Louis, Missouri 63104 |
| University of New Mexico Cancer Research and Treatment Center | Albuquerque, New Mexico 87131 |
| Schneider Children's Hospital | New Hyde Park, New York 11042 |
| St. Christopher's Hospital for Children | Philadelphia, Pennsylvania 19134-1095 |
| St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
| Driscoll Children's Hospital | Corpus Christi, Texas 78466 |
| Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
| Inova Fairfax Hospital | Falls Church, Virginia 22042-3300 |
| UCSF Comprehensive Cancer Center | San Francisco, California 94115 |
| Fletcher Allen Health Care - University Health Center Campus | Burlington, Vermont 05401 |
| Phoenix Children's Hospital | Phoenix, Arizona 85016-7710 |
| Southern California Permanente Medical Group | Downey, California 90242 |
| Southern Illinois University School of Medicine | Springfield, Illinois 62794-9658 |
| Kosair Children's Hospital | Louisville, Kentucky 40202-3830 |
| Sunrise Hospital and Medical Center | Las Vegas, Nevada 89109-2306 |
| Brooklyn Hospital Center | Brooklyn, New York 11201 |
| Children's Hospital Medical Center of Akron | Akron, Ohio 44308 |
| Children's Medical Center - Dayton | Dayton, Ohio 45404 |
| Palmetto Health South Carolina Cancer Center | Columbia, South Carolina 29203 |
| East Tennessee Children's Hospital | Knoxville, Tennessee 37901 |
| Children's Hospital of Austin | Austin, Texas 78701 |
| Children's Hospital of the King's Daughters | Norfolk, Virginia 23507 |
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
| Markey Cancer Center at University of Kentucky Chandler Medical Center | Lexington, Kentucky 40536-0084 |
| Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
| Overlook Hospital | Summit, New Jersey 07902-0220 |
| Winthrop University Hospital | Mineola, New York 11501 |
| Loma Linda University Cancer Institute at Loma Linda University Medical Center | Loma Linda, California 92354 |
| Jonathan Jaques Children's Cancer Center at Miller Children's Hospital | Long Beach, California 90801 |
| Kaiser Permanente Medical Center - Oakland | Sacramento, California 95825 |
| Children's Hospital and Health Center - San Diego | San Diego, California 92123-4282 |
| Lee Cancer Care of Lee Memorial Health System | Fort Myers, Florida 33901 |
| Broward General Medical Center Cancer Center | Ft. Lauderdale, Florida 33316 |
| University of Florida Shands Cancer Center | Gainesville, Florida 32610-0232 |
| Florida Hospital Cancer Institute at Florida Hospital Orlando | Orlando, Florida 32803-1273 |
| Sacred Heart Cancer Center at Sacred Heart Hospital | Pensacola, Florida 32504 |
| St. Joseph's Cancer Institute at St. Joseph's Hospital | Tampa, Florida 33607 |
| Kaplan Cancer Center at St. Mary's Medical Center | West Palm Beach, Florida 33407 |
| Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
| Advocate Christ Medical Center | Oak Lawn, Illinois 60453 |
| St. Vincent Indianapolis Hospital | Indianapolis, Indiana 46260 |
| Blank Children's Hospital | Des Moines, Iowa 50309 |
| Ochsner Cancer Institute at Ochsner Clinic Foundation | New Orleans, Louisiana 70121 |
| CancerCare of Maine at Eastern Maine Medial Center | Bangor, Maine 04401 |
| Breslin Cancer Center at Ingham Regional Medical Center | Lansing, Michigan 48910 |
| Hackensack University Medical Center Cancer Center | Hackensack, New Jersey 07601 |
| Albert Einstein Cancer Center at Albert Einstein College of Medicine | Bronx, New York 10461 |
| NYU Cancer Institute at New York University Medical Center | New York, New York 10016 |
| SUNY Upstate Medical University Hospital | Syracuse, New York 13210 |
| Presbyterian Cancer Center at Presbyterian Hospital | Charlotte, North Carolina 28233-3549 |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
| Rainbow Babies and Children's Hospital | Cleveland, Ohio 44106-5000 |
| Toledo Hospital | Toledo, Ohio 43606 |
| Legacy Emanuel Hospital and Health Center & Children's Hospital | Portland, Oregon 97227 |
| Rhode Island Hospital Comprehensive Cancer Center | Providence, Rhode Island 02903 |
| Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
| Texas Tech University Health Sciences Center School of Medicine - Amarillo | Amarillo, Texas 79106 |
| Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
| Baylor University Medical Center - Houston | Houston, Texas 77030-2399 |
| Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
| Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
| Carilion Cancer Center of Western Virginia | Roanoke, Virginia 24029 |
| Providence Cancer Center at Sacred Heart Medical Center | Spokane, Washington 99220-2555 |
| Edwards Comprehensive Cancer Center at Cabell Huntington Hospital | Huntington, West Virginia 25701 |
| Saint Peter's University Hospital | New Brunswick, New Jersey 08901-1780 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
| Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center | Los Angeles, California 90048-1865 |
| Childrens Hospital Los Angeles | Los Angeles, California 90027 |
| Alfred I. duPont Hospital for Children | Wilmington, Delaware 19803 |
| MBCCOP - Medical College of Georgia Cancer Center | Augusta, Georgia 30912-3730 |
| Advocate Lutheran General Cancer Care Center | Park Ridge, Illinois 60068-1174 |
| Indiana University Melvin and Bren Simon Cancer Center | Indianapolis, Indiana 46202-5289 |
| Tulane Cancer Center Office of Clinical Research | Alexandria, Louisiana 71315-3198 |
| Maine Children's Cancer Program at Barbara Bush Children's Hospital | Scarborough, Maine 04074-9308 |
| Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
| University of Mississippi Cancer Clinic | Jackson, Mississippi 39216-4505 |
| Children's Hospital | Omaha, Nebraska 68114-4113 |
| Albany Medical Center Hospital | Albany, New York 12208-3419 |
| Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center | New York, New York 10032 |
| Tod Children's Hospital | Youngstown, Ohio 44501 |
| Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
| Virginia Commonwealth University Massey Cancer Center | Richmond, Virginia 23298-0037 |
| Madigan Army Medical Center - Tacoma | Tacoma, Washington 98431 |
| Spectrum Health Hospital - Butterworth Campus | Grand Rapids, Michigan 49503 |
| Children's Hospital Cancer Center | Denver, Colorado 80218 |
| Columbus Children's Hospital | Columbus, Ohio 43205-2696 |
| Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |
| Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham | Birmingham, Alabama 35294 |
| Stanford Comprehensive Cancer Center - Stanford | Stanford, California 94305 |
| University of Minnesota Children's Hospital - Fairview | Minneapolis, Minnesota 55455 |
| Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center | Lebanon, New Hampshire 03756-0002 |
| Memorial Sloan - Kettering Cancer Center | New York, New York 10021 |
| Children's Hospital & Research Center Oakland | Oakland, California 94609 |
