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

July 25, 2014 updated by: Children's Oncology Group

Treatment of High Risk Central Nervous System Embryonal Tumors With Conventional Radiotherapy and Intensive Consolidation Chemotherapy With Peripheral Blood Progenitor Cell (PBSC) Support

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
See detailed description.
Other Names:
  • CBDCA
  • Paraplatin®
  • NSC#241240
Other Names:
  • CPM
  • Cytoxan®
  • Neosar®
  • Procytox®
Other Names:
  • TRIETHYLENETHIOPHOSPHORAMIDE
  • THIOPLEX®
  • TEPA
  • NSC# 6396
Other Names:
  • VCR
  • Vincasar®
  • Oncovin®
  • leucocristine
  • NSC# 67574
Other Names:
  • G-CSF
  • Neupogen®
  • NSC#614629

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Event Free Survival

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: H. Stacy Nicholson, MD, MPH, OHSU Knight Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 1999

Primary Completion (Actual)

October 1, 2004

Study Completion (Actual)

March 1, 2007

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

May 24, 2004

First Posted (Estimate)

May 25, 2004

Study Record Updates

Last Update Posted (Estimate)

July 28, 2014

Last Update Submitted That Met QC Criteria

July 25, 2014

Last Verified

July 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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