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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


Phase 3
N/A
20 Years
Not Enrolling
Both
Brain Tumor, Central Nervous System Tumor

Thank you

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 InstituteBuffalo, New York  14263
Emory University Hospital - AtlantaAtlanta, Georgia  30322
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
New York Medical CollegeValhalla, New York  10595
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
University of Miami Sylvester Comprehensive Cancer CenterMiami, Florida  33136
Siteman Cancer Center at Barnes-Jewish HospitalSaint Louis, Missouri  63110
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
University of California Davis Cancer CenterSacramento, California  95817
Nemours Children's ClinicJacksonville, Florida  32207
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Children's Hospital Medical Center of AkronAkron, Ohio  44308
Children's Medical Center - DaytonDayton, Ohio  45404
Covenant Children's HospitalLubbock, Texas  79410
Children's Hospital of the King's DaughtersNorfolk, Virginia  23507
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Herbert Irving Comprehensive Cancer Center at Columbia UniversityNew York, New York  10032
Fairview University Medical Center - University CampusMinneapolis, Minnesota  55455
Oklahoma University Medical CenterOklahoma City, Oklahoma  73104
Sioux Valley Hospital and University of South Dakota Medical CenterSioux Falls, South Dakota  57117-5134
Children's Hospital and Research Center - OaklandOakland, California  94609-1809
Children's Hospital and Health Center - San DiegoSan Diego, California  92123-4282
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
Kaplan Cancer Center at St. Mary's Medical CenterWest Palm Beach, Florida  33407
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
CancerCare of Maine at Eastern Maine Medial CenterBangor, Maine  04401
Floating Hospital for Children at Tufts - New England Medical CenterBoston, Massachusetts  02111
Spectrum Health Cancer Care - Butterworth CampusGrand Rapids, Michigan  49503-2560
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Massey Cancer Center at Virginia Commonwealth UniversityRichmond, Virginia  23298-0037
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
Children's Hospital Cancer CenterDenver, Colorado  80218
Columbus Children's HospitalColumbus, Ohio  43205-2696
Children's Hospital of Minnesota - MinneapolisMinneapolis, Minnesota  55404