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


Phase 2
3 Years
21 Years
Open (Enrolling)
Both
Brain and Central Nervous System Tumors, Neuroblastoma

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

H. Stacy Nicholson, MD, MPH

Investigator Role:

Study Chair

Investigator Affiliation:

OHSU Knight Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000067006

NCT ID:

NCT00003846

Start Date:

July 1999

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Neuroblastoma
  • regional neuroblastoma
  • disseminated neuroblastoma
  • stage 4S neuroblastoma
  • untreated childhood supratentorial primitive neuroectodermal tumor
  • untreated childhood medulloblastoma
  • newly diagnosed childhood ependymoma
  • Nervous System Neoplasms
  • Neuroblastoma
  • Central Nervous System Neoplasms
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Texas - MD Anderson Cancer CenterHouston, Texas  77030-4009
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
University of Minnesota Cancer CenterMinneapolis, Minnesota  55455
NYU School of Medicine's Kaplan Comprehensive Cancer CenterNew York, New York  10016
Oregon Cancer Center at Oregon Health Sciences UniversityPortland, Oregon  97201-3098
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital of Orange CountyOrange, California  92668
Children's Hospital of DenverDenver, Colorado  80218
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Hospital Medical Center - CincinnatiCincinnati, Ohio  45229-3039
Children's Hospital of ColumbusColumbus, Ohio  43205-2696