Radiation Therapy, Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With Primitive Neuroectodermal Tumors - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003846

Purpose

RATIONALE: Radiation therapy uses x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of radiation therapy and chemotherapy and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of radiation therapy, chemotherapy and peripheral stem cell transplantation in treating patients with primitive neuroectodermal tumors.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors Neuroblastoma	Drug: carboplatin Drug: cyclophosphamide Drug: filgrastim Drug: thiotepa Drug: vincristine sulfate Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation Procedure: radiation therapy	Phase II

MedlinePlus related topics: Cancer Neuroblastoma

Drug Information available for: Cyclophosphamide Carboplatin Filgrastim Vincristine sulfate Vincristine Thiotepa

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Treatment of High Risk Central Nervous System Embryonal Tumors With Conventional Radiotherapy and Intensive Consolidation Chemotherapy With Peripheral Blood Progenitor Cell (PBSC) Support

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

Estimated Enrollment:	56
Study Start Date:	July 1999

Detailed Description:

OBJECTIVES:

Determine the safety of postradiotherapy high-dose consolidation chemotherapy with peripheral blood stem cell (PBSC) support in patients with high-risk primitive neuroectodermal tumors.
Determine the safety of delaying radiotherapy by approximately one month in these patients.
Determine the maximum tolerated dose of thiotepa in these patients.
Determine the toxic effects of intensive chemotherapy with PBSC support in these patients.
Assess the time to hematopoietic recovery after PBSC infusion when intensive chemotherapy is used after craniospinal radiotherapy in these patients.
Determine the overall and event-free survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of thiotepa during consolidation therapy.

Induction: Within 31 days of initial surgery, patients receive induction therapy comprising vincristine IV on day 0, cyclophosphamide IV over 2 hours on days 0 and 1, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 2 and continuing for at least 7-10 days. Peripheral blood stem cells (PBSC) are then collected.
Chemoradiotherapy: After blood cell counts recover, and within 28 days of starting induction, patients begin chemoradiotherapy. Patients receive vincristine IV once weekly for 8 doses. Radiotherapy is administered 5 days a week, for 6 weeks, beginning within the same week as the start of vincristine.
Consolidation: Therapy begins 4-6 weeks after the last radiation treatment in the absence of disease progression. The first and third course are the same and comprise vincristine IV on day 0, carboplatin IV over 1 hour on days 0 and 1, thiotepa IV over 3 hours on days 2-4, and G-CSF SC daily beginning on day 7. PBSC are reinfused on day 7. The second course comprises vincristine IV on day 0, carboplatin IV over 1 hour on days 0 and 1, cyclophosphamide IV over 2 hours on days 2 and 3, and G-CSF SC daily beginning on day 5. PBSC are reinfused on day 5. Each course lasts 21 days.

For consolidation therapy, cohorts of 6-12 patients each receive escalating doses of thiotepa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 2 of 12 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 24-56 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	3 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically proven primitive neuroectodermal tumor (PNET) of one of the following types:
- Atypical teratoid/rhabdoid tumor
- Medulloblastoma
- Desmoplastic medulloblastoma
- Ependymoblastoma
- Medullomyoblastoma
- Spongioblastoma
- Spongioblastoma polare
- Primitive polar spongioblastoma
- Medulloepithelioma
- Neuroblastoma
- Pineoblastoma
Posterior fossa PNET must be M1-3 or M0 with greater than 1.5 cm2 residual disease
Nonposterior fossa PNET and other types must be M0-3
- If M3, must show clear evidence of tumor on MRI
No marrow involvement or other extraneural metastases
No M4 disease
No cord compression requiring emergency radiotherapy

PATIENT CHARACTERISTICS:

Age:

3 to 21

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 1,000/mm^3
Platelet count at least 150,000/mm^3 (no platelet transfusions)
Hemoglobin at least 10 g/dL (red blood cell transfusions allowed)

Hepatic:

Bilirubin less than 1.5 times upper limit of normal (ULN)
AST or ALT less than 2.5 times ULN

Renal:

Creatinine clearance or glomerular filtration rate at least 70 mL/min

Cardiovascular:

Shortening fraction greater than 27% by echocardiogram OR
Ejection fraction greater than 47% by MUGA

Pulmonary:

FEV_1/FVC greater than 60% except for children who:
- Are uncooperative
- Have no dypsnea at rest
- Have no exercise intolerance
- Have pulse oximetry greater than 94% on room air

Other:

Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

Not specified

Endocrine therapy:

Steroids for increased intracranial pressure allowed

Radiotherapy:

See Disease Characteristics
No prior urgent radiotherapy

Surgery:

Not specified

Other:

No prior therapy for tumor

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003846

Locations

United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
Children's Hospital of Orange County
Orange, California, United States, 92668
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
United States, Colorado
Children's Hospital of Denver
Denver, Colorado, United States, 80218
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
United States, Ohio
Children's Hospital Medical Center - Cincinnati
Cincinnati, Ohio, United States, 45229-3039
Children's Hospital of Columbus
Columbus, Ohio, United States, 43205-2696
United States, Oregon
Oregon Cancer Center at Oregon Health Sciences University
Portland, Oregon, United States, 97201-3098
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

H. Stacy Nicholson, MD, MPH

Oregon Health and Science University Cancer Institute

More Information

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

Study ID Numbers:	CDR0000067006, COG-99702, CCG-99702
Study First Received:	November 1, 1999
Last Updated:	August 23, 2008
ClinicalTrials.gov Identifier:	NCT00003846
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma

untreated childhood supratentorial primitive neuroectodermal tumor
untreated childhood medulloblastoma
newly diagnosed childhood ependymoma

Study placed in the following topic categories:

Neuroectodermal Tumors, Primitive
Vincristine
Carboplatin
Central Nervous System Neoplasms
Cyclophosphamide
Neuroblastoma
Ependymoma
Thiotepa

Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Medulloblastoma
Neuroepithelioma
Nervous System Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Mitosis Modulators
Nervous System Diseases
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Antimitotic Agents
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 14, 2009