Clinical trial NCT00003846: Radiation Therapy, Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With Primitive Neuroectodermal Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Neuroblastoma
Keywords: regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma
untreated childhood supratentorial primitive neuroectodermal tumor
untreated childhood medulloblastoma
newly diagnosed childhood ependymoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-05-25
Enrollment: 25
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Event Free Survival
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Denver
country: United States
facility: Children's Hospital of Denver
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center - Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Children's Hospital of Columbus
state: Ohio
city: Portland
country: United States
facility: Oregon Cancer Center at Oregon Health Sciences University
state: Oregon
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: OHSU Knight Cancer Institute
name: H. Stacy Nicholson, MD, MPH
role: STUDY_CHAIR
References: