A Phase III Randomized Trial for the Treatment of Pediatric High Grade Gliomas at First Recurrence With a Single High Dose Chemotherapy and Autologous Stem Cell Transplant Versus Three Courses of Intermediate Dose Chemotherapy With Peripheral Blood Stem Cell (PBSC) Support
N/A
20 Years
Both
Brain Tumor, Central Nervous System Tumor
Trial Information
A Phase III Randomized Trial for the Treatment of Pediatric High Grade Gliomas at First Recurrence With a Single High Dose Chemotherapy and Autologous Stem Cell Transplant Versus Three Courses of Intermediate Dose Chemotherapy With Peripheral Blood Stem Cell (PBSC) Support
OBJECTIVES:
- Compare the event-free survival and overall survival of pediatric patients with
recurrent high-grade gliomas treated with a single course of high-dose carboplatin,
etoposide, and thiotepa and autologous stem cell transplantation vs multiple courses of
intermediate-dose carboplatin and thiotepa and autologous stem cell transplantation
with or without isotretinoin.
- Compare the number of hospital days and time to engraftment in patients treated with
these regimens.
- Compare the toxic death rate in patients treated with these regimens.
- Compare the tolerability of isotretinoin in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
pathologic diagnosis (glioblastoma multiforme vs anaplastic astrocytoma vs other high-grade
glioma).
- Chemotherapy and autologous stem cell reinfusion (ASCR): Patients are randomized to 1
of 2 treatment arms.
- Arm I (high-dose chemotherapy and ASCR): Patients receive high-dose chemotherapy
comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours
and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or
subcutaneously (SC) once daily beginning on day 1 and continuing until blood
counts recover. Autologous peripheral blood stem cells (PBSC) or bone marrow are
reinfused on day 0.
- Arm II (intermediate-dose chemotherapy and ASCR): Patients receive
intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa
IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and
continuing until blood counts recover. Autologous PBSC or bone marrow are
reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses.
- Maintenance therapy: After recovery from chemotherapy (approximately day 30
post-transplantation), all patients are further randomized to 1 of 2 maintenance arms.
- Arm I: Patients receive oral isotretinoin twice daily on days 1-14. Treatment
repeats every 28 days for a total of 6 courses.
- Arm II: Patients do not receive maintenance therapy. In all arms, treatment
continues in the absence of disease progression.
Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then
annually thereafter.
PROJECTED ACCRUAL: A total of 80-150 patients (40-75 per treatment arm) will be accrued for
this study within 5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following high-grade gliomas:
- Glioblastoma multiforme
- Anaplastic astrocytoma
- Gliosarcoma
- Disease in first relapse
- No primary brainstem or spinal cord gliomas
- No secondary glioblastomas arising after prior treatment for a non-glial tumor
- Prior local radiotherapy of 5,000-6,000 cGy required
- Less than 1.5 cm of residual gadolinium-enhancing tumor in maximal cross-sectional
diameter by MRI
- No metastatic tumor by spinal MRI
PATIENT CHARACTERISTICS:
Age
- Under 21 at diagnosis
Performance status
- Lansky 50-100% OR
- Karnofsky 50-100%
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 500/mm^3
- Platelet count ≥ 100,000/mm^3 (transfusion independent)
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST or ALT < 2.5 times ULN
Renal
- Glomerular filtration rate ≥ 60 mL/min AND/OR
- Creatinine clearance ≥ 60 mL/min
Cardiovascular
- Shortening fraction ≥ 27% by echocardiogram OR
- Ejection fraction ≥ 50% by MUGA
Pulmonary
- No dyspnea at rest
- No exercise intolerance
- Pulse oximetry > 94%
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- More than 4 weeks since prior chemotherapy
- No prior thiotepa
- No prior myeloablative chemotherapy
Endocrine therapy
- No concurrent corticosteroids
Radiotherapy
- See Disease Characteristics
- More than 8 weeks since prior radiotherapy
- No prior craniospinal radiotherapy
Surgery
- Not specified
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Event-free survival
Outcome Description:
The primary endpoint for the evaluation of treatment efficacy will be event-free survival (EFS)
Outcome Time Frame:
om study entry to disease progression, disease relapse, occurrence of a second malignant neoplasm, or death from any cause. assessed up to 4 years
Safety Issue:
No
Principal Investigator
Ziad Khatib, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Miami Children's Hospital
Authority:
United States: Federal Government
Study ID:
ACNS0231
NCT ID:
NCT00078988
Start Date:
October 2004
Completion Date:
September 2006
Related Keywords:
- Brain Tumor
- Central Nervous System Tumor
- childhood high-grade cerebral astrocytoma
- recurrent childhood cerebellar astrocytoma
- recurrent childhood cerebral astrocytoma
- Brain Neoplasms
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Emory University Hospital - Atlanta | Atlanta, Georgia 30322 |
| Indiana University Cancer Center | Indianapolis, Indiana 46202-5265 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
| Van Elslander Cancer Center at St. John Hospital and Medical Center | Grosse Pointe Woods, Michigan 48236 |
| Penn State Cancer Institute at Milton S. Hershey Medical Center | Hershey, Pennsylvania 17033-0850 |
| Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
| New York Medical College | Valhalla, New York 10595 |
| University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
| University of Miami Sylvester Comprehensive Cancer Center | Miami, Florida 33136 |
| Siteman Cancer Center at Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| Cancer Research Center of Hawaii | Honolulu, Hawaii 96813 |
| Children's National Medical Center | Washington, District of Columbia 20010-2970 |
| Children's Mercy Hospital | Kansas City, Missouri 64108 |
| University of California Davis Cancer Center | Sacramento, California 95817 |
| Nemours Children's Clinic | Jacksonville, Florida 32207 |
| Miami Children's Hospital | Miami, Florida 33155-4069 |
| All Children's Hospital | St. Petersburg, Florida 33701 |
| Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
| Inova Fairfax Hospital | Falls Church, Virginia 22042-3300 |
| Kosair Children's Hospital | Louisville, Kentucky 40202-3830 |
| Children's Hospital Medical Center of Akron | Akron, Ohio 44308 |
| Children's Medical Center - Dayton | Dayton, Ohio 45404 |
| Covenant Children's Hospital | Lubbock, Texas 79410 |
| 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 |
| Herbert Irving Comprehensive Cancer Center at Columbia University | New York, New York 10032 |
| Fairview University Medical Center - University Campus | Minneapolis, Minnesota 55455 |
| Oklahoma University Medical Center | Oklahoma City, Oklahoma 73104 |
| Sioux Valley Hospital and University of South Dakota Medical Center | Sioux Falls, South Dakota 57117-5134 |
| Children's Hospital and Research Center - Oakland | Oakland, California 94609-1809 |
| Children's Hospital and Health Center - San Diego | San Diego, California 92123-4282 |
| University of Florida Shands Cancer Center | Gainesville, Florida 32610-0232 |
| 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 |
| St. Vincent Indianapolis Hospital | Indianapolis, Indiana 46260 |
| CancerCare of Maine at Eastern Maine Medial Center | Bangor, Maine 04401 |
| Floating Hospital for Children at Tufts - New England Medical Center | Boston, Massachusetts 02111 |
| Spectrum Health Cancer Care - Butterworth Campus | Grand Rapids, Michigan 49503-2560 |
| NYU Cancer Institute at New York University Medical Center | New York, New York 10016 |
| SUNY Upstate Medical University Hospital | Syracuse, New York 13210 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Rainbow Babies and Children's Hospital | Cleveland, Ohio 44106-5000 |
| Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
| Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
| Massey Cancer Center at Virginia Commonwealth University | Richmond, Virginia 23298-0037 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
| Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | New Brunswick, New Jersey 08903 |
| Children's Hospital Cancer Center | Denver, Colorado 80218 |
| Columbus Children's Hospital | Columbus, Ohio 43205-2696 |
| Children's Hospital of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
