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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00003846
First received: November 1, 1999
Last updated: July 25, 2014
Last verified: July 2014
  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
Biological: filgrastim
Drug: carboplatin
Drug: cyclophosphamide
Drug: thiotepa
Drug: vincristine sulfate
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event Free Survival [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: July 1999
Study Completion Date: March 2007
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
See detailed description.
Biological: filgrastim
Other Names:
  • Neupogen®
  • G-CSF
  • NSC#614629
Drug: carboplatin
Other Names:
  • Paraplatin®
  • CBDCA
  • NSC#241240
Drug: cyclophosphamide
Other Names:
  • Cytoxan®
  • Neosar®
  • Procytox®
  • CPM
Drug: thiotepa
Other Names:
  • TRIETHYLENETHIOPHOSPHORAMIDE
  • THIOPLEX®
  • TEPA
  • NSC# 6396
Drug: vincristine sulfate
Other Names:
  • Oncovin®
  • Vincasar®
  • leucocristine
  • VCR
  • NSC# 67574
Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy

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
  • Non posterior 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 dyspnea 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
Children's Hospital of Orange County
Orange, California, United States, 92668
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
Investigators
Study Chair: H. Stacy Nicholson, MD, MPH OHSU Knight Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00003846     History of Changes
Other Study ID Numbers: 99702, COG-99702, CCG-99702, CDR0000067006
Study First Received: November 1, 1999
Last Updated: July 25, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma
untreated childhood supratentorial primitive neuroectodermal tumor
untreated childhood medulloblastoma
newly diagnosed childhood ependymoma

Additional relevant MeSH terms:
Neoplasms
Neuroblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Cyclophosphamide
Thiotepa
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Tubulin Modulators

ClinicalTrials.gov processed this record on September 18, 2014