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

Phase 2

Completed

• Conditions: Neuroblastoma; Brain and Central Nervous System Tumors
• Interventions: Biological: filgrastim; Drug: carboplatin; Drug: cyclophosphamide; Drug: thiotepa; Drug: vincristine sulfate; Procedure: bone marrow ablation with stem cell support; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

• Registration Number: NCT00003846
• Lead Sponsor: Children's Oncology Group

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.

Study Timeline

• Study Start: 1999-07
• Study First Submitted: 1999-11-01
• Study First Submitted QC: 2004-05-24
• Study First Posted: 2004-05-25
• Primary Completion: 2004-10
• Study Completion: 2007-03
• Status Verified: 2014-07
• Last Update Submitted: 2014-07-25
• Last Update Posted: 2014-07-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	filgrastim	See detailed description.
Treatment	cyclophosphamide	See detailed description.
Treatment	vincristine sulfate	See detailed description.
Treatment	radiation therapy	See detailed description.
Treatment	bone marrow ablation with stem cell support	See detailed description.
Treatment	peripheral blood stem cell transplantation	See detailed description.
Treatment	carboplatin	See detailed description.
Treatment	thiotepa	See detailed description.

Primary Outcome Measures

Name	Time	Method
Event Free Survival

Trial Locations

Locations (13)

Jonsson Comprehensive Cancer Center, UCLA; 🇺🇸 Los Angeles, California, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Minnesota Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States

Children's Hospital Medical Center - Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

Children's Hospital of Denver; 🇺🇸 Denver, Colorado, United States

NYU School of Medicine's Kaplan Comprehensive Cancer Center; 🇺🇸 New York, New York, United States

Oregon Cancer Center at Oregon Health Sciences University; 🇺🇸 Portland, Oregon, United States

University of Texas - MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Children's Hospital of Columbus; 🇺🇸 Columbus, Ohio, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States