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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00003141
First received: November 1, 1999
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Intensive Chemotherapy With Peripheral Stem Cell Support for Infants With Malignant Brain Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Feasibility [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]
    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

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

  • Overall rates of significant toxicities including grade IV ototoxicity, electrolytic wasting (grade IV), and hemorrhagic cystitis (grade IV) [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 94
Study Start Date: March 1998
Study Completion Date: October 2011
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Filgrastim
Drug: carboplatin
Given IV
Other Names:
  • Paraplatin
  • CBDCA
  • 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

Detailed Description:

OBJECTIVES:

  • 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.

  Eligibility

Ages Eligible for Study:   up to 2 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • 6 months to less than 3 years

Performance Status:

  • Not specified

Life Expectancy:

  • More than 8 weeks

Hematopoietic:

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

Hepatic:

  • Bilirubin less than 2.0 mg/dL

Renal:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior biologic therapy

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • Prior corticosteroids allowed

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • No more than 6 weeks since prior surgery
  • Recovered from prior surgery (stable)
  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: NCT00003141

  Show 71 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Bruce H. Cohen, MD The Cleveland Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00003141     History of Changes
Other Study ID Numbers: 99703, COG-99703, CCG-99703, CDR0000065924
Study First Received: November 1, 1999
Last Updated: March 27, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
childhood high-grade cerebral astrocytoma
childhood choroid plexus tumor
untreated childhood brain stem glioma
untreated childhood supratentorial primitive neuroectodermal tumor
childhood spinal cord neoplasm
childhood atypical teratoid/rhabdoid tumor
childhood low-grade cerebral astrocytoma
childhood central nervous system embryonal tumor
childhood central nervous system mixed germ cell tumor
childhood central nervous system yolk sac tumor
childhood infratentorial ependymoma
childhood supratentorial ependymoma
disseminated neuroblastoma
stage 4S neuroblastoma
embryonal childhood rhabdomyosarcoma
previously untreated childhood rhabdomyosarcoma
untreated childhood cerebellar astrocytoma
untreated childhood medulloblastoma
newly diagnosed childhood ependymoma
localized resectable neuroblastoma
localized unresectable neuroblastoma
regional neuroblastoma
childhood central nervous system choriocarcinoma
childhood central nervous system germinoma
childhood central nervous system teratoma

Additional relevant MeSH terms:
Brain Neoplasms
Nervous System Neoplasms
Spinal Cord Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Spinal Cord Diseases
Neoplasms, Connective and Soft Tissue
Neuroblastoma
Sarcoma
Central Nervous System Diseases
Nervous System Diseases
Etoposide phosphate
Cisplatin
Cyclophosphamide
Etoposide
Thiotepa
Vincristine
Carboplatin
Lenograstim
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2014