Radiation Therapy and Combination Chemotherapy in Treating Young Patients With Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Ependymoma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Multicenter Therapy Optimizing Study for Treatment of Children and Adolescents With Intracranial Medulloblastoma / PNET and Ependymoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00303810
• Other study ID #: CDR0000455572
• Secondary ID: GPOH-HIT-2000EU-
• Status: Completed
• Phase: N/A
• First received: March 15, 2006
• Last updated: January 27, 2014
• Start date: January 2001

Study information

• Verified date: July 2009
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy in different ways and giving it together with more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which radiation therapy and combination chemotherapy regimen is more effective in treating medulloblastoma, supratentorial primitive neuroectodermal tumor (PNET), or ependymoma.

PURPOSE: This clinical trial is studying six different radiation therapy and combination chemotherapy regimens to compare how well they work in treating young patients with medulloblastoma, PNET, or ependymoma.

Description:

OBJECTIVES:

• Compare prognosis, using adapted risk stratification and quality control of diagnostic assessments and therapy, in pediatric patients with intracranial medulloblastoma, supratentorial primitive neuroectodermal tumor (PNET), or ependymoma treated with intensified chemotherapy and radiotherapy.

• Determine the effect of omission of radiotherapy, in terms of long-term sequelae, in young children with medulloblastoma and by hyperfractionation and reduction of radiotherapy in older children with medulloblastoma.

• Compare hyperfractionated radiotherapy with reduced-dose radiotherapy in older children with stage M0 medulloblastoma.

OUTLINE: This is a multi-protocol study. Patients are enrolled on 1 of 6 treatment protocols according to diagnosis and age at diagnosis.

• Protocol HIT-2000-AB4 (≥ 4 years old at diagnosis with nonmetastatic medulloblastoma)(phase III randomized controlled multicenter study): Patients are randomized to undergo hyperfractionated radiotherapy or conventional reduced-dose radiotherapy, followed by vincristine, lomustine, and cisplatin.

• Protocol HIT-2000-BIS4 (< 4 years old at diagnosis with nonmetastatic medulloblastoma):

Patients receive 5 courses of cyclophosphamide, vincristine, methotrexate, carboplatin, etoposide phosphate, and intrathecal methotrexate. Patients with residual tumors after 3 courses undergo conventionally fractionated reduced-dose radiotherapy.

• Protocol MET-HIT-2000-AB4 (≥ 4 years old at diagnosis with metastatic medulloblastoma or supratentorial PNET): Patients receive combination chemotherapy as in HIT-2000-BIS4 for 2 courses. Patients then undergo hyperfractionated radiotherapy and receive combination chemotherapy as in HIT-2000-AB4. Patients with good response to combination chemotherapy (as in HIT-2000-BIS4) also receive high-dose chemotherapy.

• Protocol MET-HIT-2000-BIS4 (< 4 years old at diagnosis with metastatic medulloblastoma or supratentorial PNET): Patients receive 2-4 courses of carboplatin IV and etoposide phosphate IV continuously over 96 hours. Patients with partial or complete response also receive high-dose carboplatin, etoposide phosphate, cyclophosphamide, and thiotepa. Patients with residual tumor undergo conventional fractionated, reduced-dose radiotherapy.

• Protocol E-HIT-2000-AB4 (≥ 4 years old at diagnosis with intracranial ependymoma):

Patients undergo local hyperfractionated radiotherapy. If histological grading shows WHO grade III tumor, patients also receive 5 courses of vincristine, cyclophosphamide, carboplatin, and etoposide phosphate.

• Protocol E-HIT-2000-BIS4 (< 4 years old at diagnosis with intracranial ependymoma):

Patients receive 5 courses of cyclophosphamide, vincristine, methotrexate IV, carboplatin, and etoposide phosphate and then undergo conventional fractionated local radiotherapy.

PROJECTED ACCRUAL: A total of 567 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 567
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

• Medulloblastoma

• Supratentorial primitive neuroectodermal tumor (PNET)

• Ependymoma

• Intracranial tumor

• No brain stem tumors

• No recurrent or relapsed tumors

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• Not specified

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• carboplatin

• cisplatin

• cyclophosphamide

• etoposide phosphate

• high-dose chemotherapy

• lomustine

• methotrexate

• thiotepa

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Germany	University Medical Center Hamburg - Eppendorf	Hamburg

Sponsors (1)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

Germany, 

References & Publications (1)

von Bueren AO, von Hoff K, Pietsch T, Gerber NU, Warmuth-Metz M, Deinlein F, Zwiener I, Faldum A, Fleischhack G, Benesch M, Krauss J, Kuehl J, Kortmann RD, Rutkowski S. Treatment of young children with localized medulloblastoma by chemotherapy alone: resu — View Citation