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Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Infants With Malignant Brain or Spinal Cord Tumors

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ClinicalTrials.gov Identifier: NCT00003141
Recruitment Status : Completed
First Posted : November 6, 2003
Last Update Posted : March 28, 2014
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctors to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating infants with malignant brain or spinal cord tumors.

Condition or disease Intervention/treatment Phase
Brain Tumors Central Nervous System Tumors Neuroblastoma Sarcoma Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Drug: thiotepa Drug: vincristine sulfate Procedure: conventional surgery Procedure: peripheral blood stem cell transplantation Phase 1

Detailed Description:


  • Determine the maximum tolerated dose of thiotepa in infants with malignant brain or spinal cord tumors receiving intensive chemotherapy.
  • Determine the feasibility and toxicity of intensive chemotherapy with peripheral blood stem cell (PBSC) rescue in these patients.
  • Assess the feasibility of harvesting PBSCs in these patients.
  • Determine the complete response rate and overall event-free survival rate in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

Patients undergo surgery for diagnosis and maximal tumor resection.

Within 6 weeks of surgery or when stable, patients begin induction chemotherapy comprising cisplatin IV over 6 hours on day 0; vincristine IV on days 0, 7, and 14; cyclophosphamide IV over 1 hour on days 1-2; and etoposide IV over 1 hour on days 0-2. Twenty four hours after the last cyclophosphamide dose, patients receive filgrastim (G-CSF) subcutaneously (SC) and undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Within 6 weeks after induction chemotherapy, patients receive consolidation chemotherapy comprising carboplatin IV over 2 hours on days 0-1 followed immediately by escalating doses of thiotepa IV over 2 hours. Patients then undergo peripheral blood stem cell transplantation 48 hours after the last thiotepa dose. Patients receive G-CSF SC daily on days 3 to 21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients experiencing dose-limiting toxicity due to thiotepa are removed from the study.

Patients are followed at 4 weeks, every 3 months for 1 year, every 6 months for 3 years, and then annually for 3 years or until relapse.

PROJECTED ACCRUAL: A total of 83 patients will be accrued for this study within 1 year.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 94 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Intensive Chemotherapy With Peripheral Stem Cell Support for Infants With Malignant Brain Tumors
Study Start Date : March 1998
Actual Primary Completion Date : December 2007
Actual Study Completion Date : October 2011

Arm Intervention/treatment
Experimental: Treatment (combination chemotherapy, PBSC transplant)
Pts undergo conventional surgery for diagnosis & max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) & undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse.
Biological: filgrastim
Given IV
Other Names:
  • r-metHuG-CSF
  • G-CSF

Drug: carboplatin
Given IV
Other Names:
  • Paraplatin
  • NSC #241240

Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • Platinol-AQ
  • NSC #119875

Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • NSC #026271

Drug: etoposide
Given IV
Other Names:
  • VP-16
  • VePesid
  • Etopophos
  • NSC #141540

Drug: thiotepa
Given IV
Other Names:
  • Tespa
  • Tspa
  • NSC #639

Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #067574

Procedure: conventional surgery
Procedure: peripheral blood stem cell transplantation

Primary Outcome Measures :
  1. Feasibility [ Time Frame: Up to 4 weeks after completion of study treatment ]
    Demonstrate the feasibility of administering this regimen, to select an acceptable Thiotepa dose for Consolidation therapy, and to document significant toxicities and estimate their overall rates

  2. Maximal tolerated dose of thiotepa for consolidation therapy [ Time Frame: 9 weeks ]
    The dose level will be assigned within 3 working days prior to beginning Consolidation.

  3. Overall rates of significant toxicities including grade IV ototoxicity, electrolytic wasting (grade IV), and hemorrhagic cystitis (grade IV) [ Time Frame: Up to 6 years ]
    Estimates will be obtained using life-table methods with an event defined as the first occurrence of toxicity. Graded using the CCG Toxicity and Complications Criteria.

Secondary Outcome Measures :
  1. Event Free Survival [ Time Frame: From the time of study entry to the first occurrence of death by any cause, progression or recurrence of disease or occurrence of a second malignant neoplasm, assessed up ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 2 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically proven malignant brain or spinal cord tumor, including the following:

    • Primitive neuroectodermal tumor
    • Ganglioneuroblastoma
    • Medulloblastoma neuroblastoma
    • Desmoplastic medulloblastoma
    • Medulloepithelioma
    • Ependymoma neuroepithelioma
    • Anaplastic ependymoma germ cell tumor
    • Astrocytoma germinoma
    • Anaplastic astrocytoma
    • Embryonal carcinoma
    • Glioblastoma endodermal sinus tumor
    • Gliosarcoma malignant teratoma
    • Choroid plexus carcinoma
    • Mixed germ cell tumor
    • Cerebellar sarcoma
    • Pineoblastoma
    • Atypical teratoid/rhabdoid tumor
    • Choriocarcinoma
    • Teratoma (malignant or with malignant transformations)
  • Diffusely involved brain stem tumors allowed if there is evidence of brain stem glioma by CT scan or MRI



  • 6 months to less than 3 years

Performance Status:

  • Not specified

Life Expectancy:

  • More than 8 weeks


  • Absolute neutrophil count greater than 1,000/mm^3
  • Platelet count greater than 100,000/mm^3


  • Bilirubin less than 2.0 mg/dL


  • Glomerular filtration rate or creatinine clearance greater than 70 mL/min


Biologic therapy:

  • No prior biologic therapy


  • No prior chemotherapy

Endocrine therapy:

  • Prior corticosteroids allowed


  • No prior radiotherapy


  • No more than 6 weeks since prior surgery
  • Recovered from prior surgery (stable)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00003141

Show Show 71 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
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Study Chair: Bruce H. Cohen, MD The Cleveland Clinic
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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00003141    
Other Study ID Numbers: 99703
COG-99703 ( Other Identifier: Children's Oncology Group )
CCG-99703 ( Other Identifier: Children's Cancer Group )
CDR0000065924 ( Other Identifier: Clinical Trials.gov )
First Posted: November 6, 2003    Key Record Dates
Last Update Posted: March 28, 2014
Last Verified: March 2014
Keywords provided by Children's Oncology Group:
childhood infratentorial ependymoma
childhood supratentorial ependymoma
disseminated neuroblastoma
stage 4S neuroblastoma
embryonal childhood rhabdomyosarcoma
childhood high-grade cerebral astrocytoma
childhood choroid plexus tumor
previously untreated childhood rhabdomyosarcoma
untreated childhood brain stem glioma
untreated childhood supratentorial primitive neuroectodermal tumor
untreated childhood cerebellar astrocytoma
untreated childhood medulloblastoma
newly diagnosed childhood ependymoma
localized resectable neuroblastoma
localized unresectable neuroblastoma
regional neuroblastoma
childhood spinal cord neoplasm
childhood atypical teratoid/rhabdoid tumor
childhood low-grade cerebral astrocytoma
childhood central nervous system choriocarcinoma
childhood central nervous system embryonal tumor
childhood central nervous system germinoma
childhood central nervous system mixed germ cell tumor
childhood central nervous system teratoma
childhood central nervous system yolk sac tumor
Additional relevant MeSH terms:
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Brain Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents