Chemotherapy, Radiation Therapy, and Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor

November 6, 2012 updated by: St. Jude Children's Research Hospital

Treatment of Newly Diagnosed Medulloblastoma and Supratentorial PNET in Patients At Least 3 Years With a Phase II Topotecan Window (High-Risk Patients Only), Risk-Adapted Radiation Therapy, and Dose-Intensive Chemotherapy With Peripheral Blood Stem Cell Support

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

PURPOSE: Phase II trial to study the effectiveness of chemotherapy with topotecan, cyclophosphamide, cisplatin, and vincristine plus radiation therapy and peripheral stem cell transplantation in treating children with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor.

Study Overview

Detailed Description

OBJECTIVES:

  • Estimate the response rate to topotecan in children with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumors who have measurable residual disease after surgery. (Topotecan window closed to accrual 9/10/2001)
  • Determine the feasibility of four courses of high-dose chemotherapy (vincristine, cisplatin, and cyclophosphamide) with peripheral blood stem cell support after craniospinal irradiation (CSI) in these patients.
  • Estimate the 5-year overall survival and progression-free survival in patients treated with risk-adapted CSI and high-dose chemotherapy.
  • Compare changes in intellectual functioning in patients treated with reduced-dose vs standard-dose CSI.
  • Estimate the incidence of ototoxicity associated with risk-adapted CSI and posterior fossa boost(s) given by 3-D conformal radiotherapy technique combined with amifostine and cisplatin.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups based on risk status.

  • Group 1 (average-risk): Patients receive filgrastim (G-CSF) subcutaneously (SC) or IV daily until peripheral blood stem cells (PBSC) are harvested. PBSC are harvested when blood counts recover. Patients then receive craniospinal irradiation (CSI) 5 days a week for 6 weeks. Beginning 6 weeks after completion of CSI, patients receive high-dose chemotherapy comprising vincristine IV followed by cisplatin IV over 6 hours on day -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Patients receive amifostine IV over 1 minute a maximum of 5 minutes prior to cisplatin infusion and then 3 hours into cisplatin infusion. PBSC are reinfused on day 0. Patients receive G-CSF SC beginning on day 1 and continuing for a minimum of 7 days or until blood counts recover. Vincristine IV is administered on day 6. G-CSF is stopped 48 hours prior to beginning subsequent courses of chemotherapy. High-dose chemotherapy repeats every 4 weeks for 4 courses.
  • Group 2 (high-risk): Patients receive topotecan IV over 4 hours on days 1-5 and G-CSF SC or IV beginning 24 hours after completion of the first course of topotecan and continuing until PBSC are harvested. Treatment repeats every 3 weeks for 2 courses. If an adequate number of PBSC are not harvested, the patient undergoes a second harvest of PBSC after the second course of topotecan. Patients then receive CSI, high-dose chemotherapy, amifostine, and PBSC support as in group 1. (Topotecan window closed to accrual 9/10/2001) Patients undergo neuropsychological testing prior to radiotherapy and chemotherapy and then at 1, 2, and 5 years.

Patients are followed at 1, 2, 4, 6, 9, 12, 15, 18, and 24 months and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 12-36 patients will be accrued for this study within 5 years.

Study Type

Interventional

Enrollment (Actual)

94

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Children's Hospital at Westmead
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Children's Hospital
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital
    • Texas
      • Houston, Texas, United States, 77030-2399
        • Texas Children's Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 20 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically proven medulloblastoma or supratentorial primitive neuroectodermal tumor
  • Average-risk group:

    • Localized tumor with no overt evidence of invasion beyond the posterior fossa
    • Less than 1.5 cm2 residual tumor/imaging abnormality
    • No CNS or extraneural metastasis (confirmed by bone scan)
    • Brain stem invasion allowed if above criteria met
  • High-risk group:

    • Metastatic disease within the neuraxis (subarachnoid dissemination) OR greater than 1.5 cm^2 residual disease at the primary site after surgery
  • No bone involvement by bone scan
  • Must begin study within 28 days of definitive surgery

PATIENT CHARACTERISTICS:

Age

  • 3 to 20 at diagnosis

Performance status

  • ECOG 0-3 (except patients with posterior fossa syndrome)

Life expectancy

  • Not specified

Hematopoietic

  • WBC greater than 3,000/mm^3
  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count greater than 100,000/mm^3
  • Hemoglobin greater than 10 g/dL

Hepatic

  • Bilirubin less than 1.5 mg/dL
  • SGPT less than 1.5 times normal

Renal

  • Creatinine less than 1.2 mg/dL OR
  • Creatinine clearance greater than 70 mL/min

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • Prior corticosteroids allowed

Radiotherapy

  • No prior radiotherapy

Surgery

  • See Disease Characteristics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SUPPORTIVE_CARE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Average-risk

Participants meeting the eligibility requirements for assignment to the average-risk arm.

Interventions: filgrastim, amifostine trihydrate, cisplatin, cyclophosphamide, vincristine sulfate, peripheral blood stem cell transplantation, radiation therapy.

Other Names:
  • PBSCT
EXPERIMENTAL: High-risk

Participants meeting the eligibility requirements for assignment to the high-risk arm.

Interventions: filgrastim, amifostine trihydrate, cisplatin, cyclophosphamide, vincristine sulfate, peripheral blood stem cell transplantation, radiation therapy.

Other Names:
  • PBSCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 1996

Primary Completion (ACTUAL)

June 1, 2007

Study Completion (ACTUAL)

June 1, 2007

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

July 8, 2003

First Posted (ESTIMATE)

July 9, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

November 7, 2012

Last Update Submitted That Met QC Criteria

November 6, 2012

Last Verified

November 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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