High-Dose Chemotherapy Plus Autologous Stem Cell Transplantation Compared With Intermediate-Dose Chemotherapy Plus Autologous Stem Cell Transplantation With or Without Isotretinoin in Treating Young Patients With Recurrent High-Grade Gliomas - Full Text View

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00078988

Purpose

RATIONALE: Drugs used in chemotherapy, such as carboplatin, thiotepa, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Isotretinoin may be effective in preventing recurrence of glioma. It is not yet known which regimen of chemotherapy plus autologous stem cell transplantation with or without isotretinoin is more effective in treating recurrent high-grade glioma.

PURPOSE: This randomized phase III trial is studying high-dose chemotherapy or intermediate-dose chemotherapy followed by autologous stem cell transplantation to see how well it works compared to high-dose chemotherapy or intermediate-dose chemotherapy followed by autologous stem cell transplantation and isotretinoin in treating young patients with recurrent high-grade glioma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Biological: filgrastim Drug: carboplatin Drug: etoposide Drug: isotretinoin Drug: thiotepa Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Bone Marrow Transplantation Cancer

Drug Information available for: Thiotepa Etoposide Carboplatin Etoposide phosphate Filgrastim Isotretinoin

U.S. FDA Resources

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

Primary Outcome Measures:

Event-free survival [ Designated as safety issue: No ]
Toxic death [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]

Study Start Date:

October 2004

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	up to 20 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00078988

Hide Study Locations

Locations

United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Children's Hospital and Health Center - San Diego
San Diego, California, United States, 92123-4282
Children's Hospital and Research Center - Oakland
Oakland, California, United States, 94609-1809
University of California Davis Cancer Center
Sacramento, California, United States, 95817
United States, Colorado
Children's Hospital Cancer Center
Denver, Colorado, United States, 80218-1088
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Florida
All Children's Hospital
St. Petersburg, Florida, United States, 33701
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States, 33407
Miami Children's Hospital
Miami, Florida, United States, 33155
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
United States, Georgia
Emory University Hospital - Atlanta
Atlanta, Georgia, United States, 30322
United States, Hawaii
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States, 95813
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
St. Vincent Indianapolis Hospital
Indianapolis, Indiana, United States, 46260
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40232
United States, Maine
CancerCare of Maine at Eastern Maine Medial Center
Bangor, Maine, United States, 04401
United States, Massachusetts
Floating Hospital for Children at Tufts - New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Spectrum Health Cancer Care - 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
United States, Minnesota
Children's Hospital of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
Fairview University Medical Center - University Campus
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Siteman Cancer Center at Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
New York Medical College
Valhalla, New York, United States, 10595
NYU Cancer Institute at New York University Medical Center
New York, New York, United States, 10016
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308-1062
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404-1815
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-5000
United States, Oklahoma
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, South Dakota
Sioux Valley Hospital and University of South Dakota Medical Center
Sioux Falls, South Dakota, United States, 57117-5039
United States, Texas
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104-9958
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113-1100
United States, Virginia
Children's Hospital of the King's Daughters
Norfolk, Virginia, United States, 23507-1971
INOVA Fairfax Hospital
Fairfax, Virginia, United States, 22031
Massey Cancer Center at Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0037
United States, Wisconsin
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, British Columbia
Children's & Women's Hospital of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Quebec
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, Canada, G1V 4G2

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Ziad Khatib, MD	Miami Children's Hospital
Investigator:	Sharon L. Gardner, MD	New York University School of Medicine

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000353207, COG-ACNS0231
Study First Received:	March 8, 2004
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00078988 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

childhood high-grade cerebral astrocytoma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma

Additional relevant MeSH terms:

Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Nervous System Diseases
Central Nervous System Neoplasms
Carboplatin
Immunosuppressive Agents
Pharmacologic Actions
Thiotepa
Neoplasms

Neoplasms by Site
Therapeutic Uses
Myeloablative Agonists
Isotretinoin
Antineoplastic Agents, Alkylating
Alkylating Agents
Dermatologic Agents
Etoposide
Antineoplastic Agents, Phytogenic
Nervous System Neoplasms

ClinicalTrials.gov processed this record on November 27, 2009