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

Phase 2

Completed

• Conditions: Brain and Central Nervous System Tumors
• Interventions: Biological: filgrastim; Drug: amifostine trihydrate; Drug: cisplatin; Drug: cyclophosphamide; Drug: vincristine sulfate; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

• Registration Number: NCT00003211
• Lead Sponsor: St. Jude Children's Research Hospital

Brief Summary

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.

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 Timeline

• Study Start: 1996-10
• Study First Submitted: 1999-11-01
• Study First Submitted QC: 2003-07-08
• Study First Posted: 2003-07-09
• Primary Completion: 2007-06
• Study Completion: 2007-06
• Status Verified: 2012-11
• Last Update Submitted: 2012-11-06
• Last Update Posted: 2012-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 94

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Average-risk	filgrastim	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.
Average-risk	amifostine trihydrate	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.
Average-risk	vincristine sulfate	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.
Average-risk	peripheral blood stem cell transplantation	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.
Average-risk	radiation therapy	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.
High-risk	filgrastim	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.
High-risk	amifostine trihydrate	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.
High-risk	cyclophosphamide	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.
High-risk	vincristine sulfate	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.
High-risk	radiation therapy	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.
High-risk	peripheral blood stem cell transplantation	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.
Average-risk	cisplatin	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.
Average-risk	cyclophosphamide	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.
High-risk	cisplatin	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.

Trial Locations

Locations (4)

Texas Children's Cancer Center; 🇺🇸 Houston, Texas, United States

Royal Children's Hospital; 🇦🇺 Parkville, Victoria, Australia

Children's Hospital at Westmead; 🇦🇺 Westmead, New South Wales, Australia

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States