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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00003211
First received: November 1, 1999
Last updated: November 6, 2012
Last verified: November 2012

November 1, 1999
November 6, 2012
October 1996
June 2007   (final data collection date for primary outcome measure)
Not Provided
Not Provided
Complete list of historical versions of study NCT00003211 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Chemotherapy, Radiation Therapy, and Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor
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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Brain and Central Nervous System Tumors
  • Biological: filgrastim
  • Drug: amifostine trihydrate
  • Drug: cisplatin
  • Drug: cyclophosphamide
  • Drug: vincristine sulfate
  • Procedure: peripheral blood stem cell transplantation
    Other Name: PBSCT
  • Radiation: radiation therapy
  • 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.

    Interventions:
    • Biological: filgrastim
    • Drug: amifostine trihydrate
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Drug: vincristine sulfate
    • Procedure: peripheral blood stem cell transplantation
    • Radiation: radiation therapy
  • 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.

    Interventions:
    • Biological: filgrastim
    • Drug: amifostine trihydrate
    • Drug: cisplatin
    • Drug: cyclophosphamide
    • Drug: vincristine sulfate
    • Procedure: peripheral blood stem cell transplantation
    • Radiation: radiation therapy

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
94
June 2007
June 2007   (final data collection date for primary outcome measure)

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
Both
3 Years to 20 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia
 
NCT00003211
CDR0000066069, SJCRH-MB-96, SJMB-96, NCI-G98-1387
No
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
National Cancer Institute (NCI)
Study Chair: Amar Gajjar, MD St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP