Combination Chemotherapy, Surgery or Radiation Therapy, and Peripheral Stem Cell Transplant in Treating Patients With Recurrent Medulloblastoma or Primitive Neuroectodermal and Pineal Tumors

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Treatment Of Recurrent Central Nervous System Primitive Neuroectodermal Tumors (PNETs) In Children And Adolescents A Strategy Including The Use Of High Dose Thiotepa And High Dose Carboplatin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00025077
• Other study ID #: CCLG-CNS-2000-01
• Secondary ID: CDR0000068910EU-
• Status: Completed
• Phase: Phase 2
• First received: October 11, 2001
• Last updated: August 1, 2013
• Start date: January 2000
• Est. completion date: April 2011

Study information

• Verified date: June 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery or radiation therapy may shrink the tumor so that it can be removed during surgery or radiation therapy. Peripheral stem cell transplant may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy and allow doctors to give higher doses of chemotherapy.

PURPOSE: This phase II trial is studying how well combination chemotherapy followed by surgery or radiation therapy and peripheral stem cell transplant work in treating patients with recurrent medulloblastoma or primitive neuroectodermal and pineal tumors.

Description:

OBJECTIVES:

• Determine the feasibility of cyclophosphamide and surgical resection or radiotherapy followed by thiotepa, carboplatin, and autologous peripheral blood stem cell rescue in patients with recurrent medulloblastoma or supratentorial neuroectodermal and pineal tumors.

• Determine the acute and chronic toxicity of this regimen in these patients.

• Determine progression-free and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Cytoreductive Phase: Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 7 and continuing until blood counts recover. Treatment repeats after discontinuation of G-CSF for 2-4 courses. Peripheral blood stem cells (PBSC) are harvested after each course of cyclophosphamide. Patients undergo surgical resection or radiotherapy after the completion of chemotherapy. Patients achieving complete response proceed to myeloablative therapy.

• Myeloablative Phase: Patients receive thiotepa IV over 3 hours on days 1-3. Autologous PBSC are reinfused on day 5 and patients receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recover. Beginning 2 days after the completion of G-CSF, patients receive carboplatin IV over 1 hour on days 1-3. Autologous PBSC are reinfused on day 5 and patients receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recover.

Patients are followed at 1, 3, 6, and 12 months.

PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study within 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 20 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed recurrent medulloblastoma or supratentorial primitive neuroectodermal and pineal tumor

• Nodular/desmoplastic medulloblastoma

• Medullomyoblastoma

• Melanotic medulloblastoma

• Ependymoblastoma

• Pinealoblastoma

• Received prior craniospinal radiotherapy OR

• Relapse in site of prior localized radiotherapy (e.g., relapse after "baby brain" protocol)

PATIENT CHARACTERISTICS:

Age:

• Under 21

Performance status:

• Lansky 40-100% for ages 1-16 years

• Karnofsky 40-100% for ages over 16 years

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Neutrophil count at least 1,000/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than upper limit of normal (ULN)

• AST less than 2 times ULN

Renal:

• Glomerular filtration rate at least 60 mL/min

Other:

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• Not specified

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Medulloblastoma
• Nervous System Neoplasms
• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive

Intervention

Biological:
• filgrastim

Drug:
• carboplatin

• cyclophosphamide

• thiotepa

Procedure:
• conventional surgery

• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Bristol Royal Hospital for Children	Bristol	England
United Kingdom	Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust	Cambridge	England
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	University College of London Hospitals	London	England
United Kingdom	Central Manchester and Manchester Children's University Hospitals NHS Trust	Manchester	England
United Kingdom	Newcastle Upon Tyne Hospitals NHS Trust	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton University Hospital NHS Trust	Southampton	England
United Kingdom	Royal Marsden NHS Foundation Trust - Surrey	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
Children's Cancer and Leukaemia Group

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival			No
Secondary	Toxic death rate			Yes