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

Sponsors and Collaborators:	Children's Oncology Group 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 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

Show 59 Study Locations

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

Study placed in the following topic categories:

Astrocytoma
Isotretinoin
Carboplatin
Glioma
Central Nervous System Neoplasms

Etoposide phosphate
Etoposide
Recurrence
Nervous System Neoplasms
Thiotepa

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Antineoplastic Agents
Therapeutic Uses
Nervous System Diseases
Isotretinoin

Carboplatin
Central Nervous System Neoplasms
Dermatologic Agents
Pharmacologic Actions
Nervous System Neoplasms

ClinicalTrials.gov processed this record on July 02, 2009